UNITED STATES COURT OF FEDERAL · PDF file2278 in the united states court of federal claims...

UNITED STATES COURT OF FEDERAL CLAIMS

_____________________________________________________________________________________ THERESA CEDILLO AND MICHAEL ) CEDILLO, AS PARENTS AND ) NATURAL GUARDIANS OF ) MICHELLE CEDILLO, ) ) Petitioners, ) ) v. ) Docket No.: 98-916V ) SECRETARY OF HEALTH AND ) HUMAN SERVICES, ) ) Respondent. )

REVISED AND CORRECTED COPY Pages: 2278 through 2495 Place: Washington, D.C. Date: June 22, 2007 _____________________________________________________________________________________ HERITAGE REPORTING CORPORATION Official Reporters 1220 L Street, N.W., Suite 600 Washington, D.C. 20005-4018 (202) 628-4888 [email protected]

Case 1:98-vv-00916-TCW Document 237 Filed 04/29/08 Page 1 of 220

2278 IN THE UNITED STATES COURT OF FEDERAL CLAIMS THERESA CEDILLO AND MICHAEL ) CEDILLO, AS PARENTS AND ) NATURAL GUARDIANS OF ) MICHELLE CEDILLO, ) ) Petitioners, ) ) v. ) Docket No.: 98-916V ) SECRETARY OF HEALTH AND ) HUMAN SERVICES, ) ) Respondent. ) Ceremonial Courtroom National Courts Building 717 Madison Place NW Washington, D.C. Friday, June 22, 2007 The parties met, pursuant to notice of the Court, at 9:00 a.m. BEFORE: HONORABLE GEORGE L. HASTINGS, JR. HONORABLE PATRICIA CAMPBELL-SMITH HONORABLE DENISE VOWELL Special Masters APPEARANCES: For the Petitioners: SYLVIA CHIN-CAPLAN, Esquire KEVIN CONWAY, Esquire Conway, Homer & Chin-Caplan, P.C. 16 Shawmut Street Boston, Massachusetts 02116 (617) 695-1990 Heritage Reporting Corporation (202) 628-4888


2279 APPEARANCES: (Cont'd.) Also for the Petitioners: CLIFFORD J. SHOEMAKER, Esquire Shoemaker & Associates 9711 Meadowlark Road Vienna, Virginia 22812 (703) 281-6395 For the Respondent: VINCENT J. MATANOSKI, Esquire TRACI R. PATTON, Esquire LINDA S. RENZI, Esquire U.S. Department of Justice Civil Division Torts Branch P.O. Box 146 Ben Franklin Station Washington, D.C. 20044-0146 (202) 616-4122 Heritage Reporting Corporation (202) 628-4888


2280 C O N T E N T S VOIR WITNESSES: DIRECT CROSS REDIRECT RECROSS DIRE For the Respondent: Nicholas Chadwick 2282 2290 -- -- -- Jeffrey Brent 2295 2372 2491 -- -- -- 2438 Heritage Reporting Corporation (202) 628-4888


2281 1 P R O C E E D I N G S 2 (9:00 a.m.) 3 SPECIAL MASTER HASTINGS: Good morning to 4 all in the courtroom and if there are any of you 5 listening in at home. 6 We had a technical breakthrough in the last 7 few hours, and we were able to work the system so that 8 we can be on phone conferencing this morning for the 9 testimony of the witness coming in by telephone from 10 England, Dr. Chadwick. 11 I apologize for the information I gave out 12 yesterday that the phone conferencing wouldn't be 13 available, but I'm glad that it is for those who are 14 able to listen. 15 With that, we've got Dr. Chadwick on the 16 line. Dr. Chadwick, can you hear me? Dr. Chadwick, 17 can you hear me? 18 DR. CHADWICK: I can, yes. 19 SPECIAL MASTER HASTINGS: Yes. This is 20 Special Master Hastings. 21 DR. CHADWICK: Hi. 22 SPECIAL MASTER HASTINGS: Hello. Good 23 morning to you. 24 DR. CHADWICK: Good morning. 25 SPECIAL MASTER HASTINGS: Or afternoon Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 perhaps where you are. 2 DR. CHADWICK: Yes. 3 SPECIAL MASTER HASTINGS: I'm going to ask 4 you, please. We're going to give you the oath for 5 testifying here. I'm going to ask you to raise your 6 right hand. 7 Whereupon, 8 NICHOLAS C. CHADWICK 9 having been duly sworn, was called as a 10 witness and was examined and testified as follows: 11 SPECIAL MASTER HASTINGS: All right. Who 12 will be doing the questioning? 13 MS. PATTON: I will be. 14 SPECIAL MASTER HASTINGS: Ms. Patton will be 15 doing the initial questioning. 16 DIRECT EXAMINATION 17 BY MS. PATTON: 18 Q Good afternoon, Dr. Chadwick. 19 A Hi. 20 Q Can you please state your name for the 21 record? 22 A Yes. Nicholas Chadwick. Nicholas Charles 23 Chadwick. 24 Q And do you recall writing a declaration for 25 this case, which you signed on May 23, 2007? Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 A Yes, I do. 2 MS. PATTON: For the record, we'll be 3 referring to Respondent's Exhibit QQ, which was filed 4 on May 25, 2007. 5 BY MS. PATTON: 6 Q Dr. Chadwick, do you swear under penalty of 7 perjury that the contents in that declaration are true 8 to the best of your knowledge? 9 A Yes, I do. 10 Q We're not going to go through the entirety 11 of your declaration, but I'm going to ask you a couple 12 questions about several portions of that declaration 13 that we'd like the Court to pay particular attention 14 to. 15 A Okay. 16 Q You stated in there that you began working 17 in Dr. Wakefield's lab at the Royal Free in 1994. Is 18 that right? 19 A Yes, that's right. 20 Q And the lab started focusing on samples and 21 testing from autistic patients in 1996? 22 A Yes. Yes. 23 Q In your affidavit you state that you were 24 present in the operating room -- I think the operating 25 theater is what it's called over there -- during Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 collection of gut biopsy material and cerebral spinal 2 fluid. Is that right? 3 A Yes, that's right. It was an endoscopy 4 suite rather than an operating theater. 5 Q And what was your role in the collection of 6 the material? 7 A My role was to take the material, bring it 8 to the lab and process it by extract RNA and then look 9 for evidence of measles RNA. 10 Q Okay. Did you personally test the gut 11 biopsy samples for measles RNA? 12 A Yes. 13 Q What tests did you perform? 14 A A PCR test, a polymerase chain reaction. 15 Q What results did you receive from the gut 16 biopsy materials for measles RNA? 17 A They were all negative. 18 Q They were always negative? 19 A Yes. There were a few cases of false 20 positive results, which I used a method to see whether 21 they were real positive results or false positive, and 22 in every case they turned out to be false positive 23 results. Essentially all the samples tested were 24 negative. 25 Q So when you say you got a positive and it Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 ended up being a false positive, what further testing 2 or what did you do to determine that those positives 3 were actually false positives? 4 A Well, we could sequence the products of the 5 PCR reaction and could find out whereabouts the virus 6 came from, and in every case it was a lab strain virus 7 based on the sequence and didn't match up with any 8 known wild-type or vaccine strains. 9 Q You sequenced wild-type that's in the lab 10 for control or to make sure your testing worked? 11 A Yes, that's right. It was just to validate 12 any positive samples. If we had a positive sample we 13 would have to sequence it to make sure it was a real 14 positive rather than a false positive. 15 Q Did you personally test CSF samples from 16 autistic children in the lab? 17 A Yes, I did. Again, they were all negative. 18 I can't recall how many I tested, but they were 19 definitely negative, the ones I did test. 20 Q Did you personally test peripheral blood 21 mononuclear cells, the PBMCs? 22 A Yes, that's right. I tested PBMC samples 23 from the blood of the autistic patients and also 24 cultured some of those blood cells in the lab to 25 enable any measles virus present to replicate and Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 become detectible, but in every case again the samples 2 proved to be negative. 3 Q So you personally tested while you were in 4 Dr. Wakefield's lab gut biopsy material, CSF and 5 PBMCs? 6 A Yes, that's right. 7 Q And all the results were either negative, or 8 if they were positive it always turned out that they 9 were false positives? 10 A Yes, that's correct. 11 Q Did you inform Dr. Wakefield of the negative 12 results? 13 A Yes. Yes. 14 Q You state in your affidavit that you sent 15 samples of RNA to Dr. Kawashima. 16 A Yes, that's right. Dr. Kawashima had been 17 working on the detection of measles virus in a 18 different disease, and Dr. Wakefield thought it would 19 be a good idea to use his methodology to see if any of 20 our samples proved positive using his methods. 21 Q Dr. Chadwick, what was your role in sending 22 the samples to Dr. Kawashima? 23 A My role was just to put the samples in test 24 tubes and randomize them, code them and randomize them 25 so that only we would know which samples were which Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 and Dr. Kawashima wouldn't know which samples he was 2 testing. 3 Q What were the results of Dr. Kawashima's 4 testing? 5 A Well, some of the samples we sent over as 6 duplicate samples so if one of them was to come up 7 positive then we would expect the other sample to come 8 up positive as well. In every case where he did have 9 a positive result then the duplicate didn't match 10 that, which led us to question his results or led me 11 to question his results. 12 When he told us that he had some positive 13 results he sent us the sequencing data back, but the 14 sequencing data matched up with the positive control 15 samples that we sent out to him, which indicated to me 16 that he had contaminated his samples and they were 17 false positive samples. 18 Q Based on the coding that you had done 19 beforehand, you knew that all of the positives that he 20 was reporting were false positives? 21 A Yes, that's right. I was pretty sure based 22 on, you know, how I'd coded the samples. 23 Q Did you tell Dr. Wakefield about the 24 problems with Dr. Kawashima's results? 25 A Yes, I did. Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 Q You state in the affidavit that during your 2 time on your Ph.D. research in Dr. Wakefield's lab you 3 only obtained nine positive PCR results for measles. 4 Every time you did that you sequenced them? 5 A That's correct, yes. We sent it off to a 6 sequencing lab to be sequenced, and the data that came 7 back showed that they were all false positive results. 8 Q Every positive result you got was a false 9 positive? 10 A Yes. Yes, apart from the case of the 11 positive control samples which we had, which were a 12 measles infection, a brain disease. We were able to 13 detect measles virus in those cases, so I was 14 confident that the methods were working fine. 15 Q Towards the end of your affidavit you state 16 that you had reservations about the 17 immunohistochemistry done to detect measles virus, 18 specifically the use of an antibody from Porton Down? 19 A Yes, that's right. The antibody seemed to 20 cross-react. 21 Experiments we did in the lab seemed to show 22 that the antibody cross-reacted with bacterial 23 proteins, which I think is an artifact of how the 24 antibody was made, and that led us or led me to think 25 that it may have been cross-reacting with bacteria in Heritage Reporting Corporation (202) 628-4888


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CHADWICK - DIRECT 1 the guts of patients rather than measles virus. 2 Q Now, that would lead to contamination? 3 A Well, it would lead to a false positive 4 result. Say for instance if the antibody was binding 5 to something in the guts of these patients, it may 6 well have been a bacteria rather than the measles 7 virus. 8 Q Okay. Producing the false positives in 9 those? 10 A Yes, that's correct. 11 Q You also state in your affidavit that you 12 believe Dr. Wakefield was aware of all of your 13 negative results when he submitted his paper, "Ileal 14 Lymphonodular Hyperplasia, Nonspecific Colitis and 15 Pervasive Developmental Disorder," which was published 16 in 1998 to the Lancet. 17 A Yes, that's correct. 18 Q You were working at the lab at that time, 19 and you had actually published some articles with Dr. 20 Wakefield on other subjects, hadn't you? 21 A Yes. Yes. 22 Q Why isn't your name on the paper I just 23 referenced? 24 A Well, my name isn't on that because none of 25 my data went into that paper. Heritage Reporting Corporation (202) 628-4888


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CHADWICK - CROSS 1 There was another manuscript which did use 2 some PCR data I think from Dr. Kawashima's lab, and I 3 asked for my name to be taken off anything that was 4 related to PCR data because I wasn't comfortable with 5 the quality of the data. 6 Q You specifically asked that your name not be 7 on that paper because of your reservations about the 8 data? 9 A Yes, that's right. 10 MS. PATTON: Thank you, Dr. Chadwick. I 11 have no further questions. 12 THE WITNESS: Thank you. 13 SPECIAL MASTER HASTINGS: Ms. Chin-Caplan, 14 any questions? 15 MS. CHIN-CAPLAN: Just a few. 16 SPECIAL MASTER HASTINGS: Please go ahead. 17 MS. CHIN-CAPLAN: Thank you. 18 CROSS-EXAMINATION 19 BY MS. CHIN-CAPLAN: 20 Q Good morning, Dr. Chadwick. My name is 21 Sylvia Chin-Caplan, and I represent the Petitioner, 22 Michelle Cedillo, in this case. 23 A Hi. 24 Q Hi. You're aware that Dr. Wakefield is not 25 a witness in this case, are you not? Heritage Reporting Corporation (202) 628-4888


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CHADWICK - CROSS 1 A I'm not aware of that. 2 Q Are you aware that the Kawashima Lab is also 3 not the lab in question here? 4 A Well, I don't know the details of the case, 5 to be honest. 6 Q When you were approached to testify in this 7 matter, what were you asked to do? 8 A I was asked to provide a statement regarding 9 the work I did for Dr. Wakefield relating to the 10 autistic patients. 11 Q And did you ask why? 12 A Sorry. I couldn't hear that last question. 13 Q Did you ask why? 14 A Did I ask why? Because it was a case 15 regarding the safety of the vaccine. 16 Q Now, you testified that you worked with 17 in-situ PCR. Is that it? 18 A Yes. This was a few years before any of the 19 autistic work was being undertaken. I did a few 20 months of working on this methodology. 21 Q In-situ PCR? 22 A Yes. I did a few months at the beginning of 23 my project with Dr. Wakefield, and I did a few months 24 at the very end as well on in-situ PCR. 25 Q So this was all on in-situ PCR? Is that Heritage Reporting Corporation (202) 628-4888


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CHADWICK - CROSS 1 correct? 2 A The work that was in my thesis relating to 3 autistic patients was using normal PCR, not in-situ 4 PCR. The in-situ PCR work I performed was never 5 written up. 6 Q I see. So the in-situ PCR is more specific 7 than the regular PCR, isn't it? 8 A No, that's not the case. 9 Q It's not? 10 A No, it's not specific. Because of the 11 methodology it's actually less specific so there's 12 less way of being certain about what is being 13 detected. 14 Q Okay. Doctor, did you at any time use 15 TaqMan PCR? 16 A No. TaqMan PCR wasn't really available 17 while I was doing the Ph.D. It was something which 18 came afterwards. 19 Q I see. Are you aware that the case that 20 we're dealing with involves TaqMan PCR? 21 A I'm not aware, no. No. 22 Q Are you aware that the lab that we're 23 dealing with involves the O'Leary Lab in Dublin, 24 Ireland? 25 A Okay. I've heard of that lab, but I didn't Heritage Reporting Corporation (202) 628-4888


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CHADWICK - CROSS 1 know that that was the lab that you were using in this 2 case. 3 Q And you've had no relationship with the 4 Dublin lab, have you? 5 A No. 6 Q You have no knowledge of their procedures or 7 the testing that was done there, do you? 8 A No. I mean, I'm aware of TaqMan PCR, but 9 that's all I know about the O'Leary Lab. 10 Q And as of the date that you left Dr. 11 Wakefield's lab, you had not utilized TaqMan PCR in an 12 experiment, had you? 13 A No. 14 Q Doctor, is there anybody with you? 15 A No. 16 Q No? You're by yourself? 17 A Yes. 18 MS. CHIN-CAPLAN: Okay. I have no further 19 questions. 20 SPECIAL MASTER HASTINGS: Any redirect? 21 MS. PATTON: No, sir. 22 SPECIAL MASTER HASTINGS: Dr. Chadwick, 23 again this is Special Master Hastings with the Court 24 in Washington. I want to thank you again for taking 25 the time to be with us. You're excused at this time. Heritage Reporting Corporation (202) 628-4888


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CHADWICK - CROSS 1 THE WITNESS: Okay. Thanks so much. 2 SPECIAL MASTER HASTINGS: Thank you, sir. 3 (Witness excused.) 4 SPECIAL MASTER HASTINGS: So, Mr. Matanoski, 5 we'll be taking Dr. Brent's testimony next? 6 MR. MATANOSKI: That's correct, sir. 7 SPECIAL MASTER HASTINGS: All right. Maybe 8 while we're getting the phone out of the way Dr. Brent 9 could take the witness stand. 10 DR. BRENT: Yes, sir. 11 (Pause.) 12 MS. RENZI: Special Master, may I? 13 SPECIAL MASTER HASTINGS: Yes, please. We 14 have now Dr. Brent in the witness chair, and Ms. Renzi 15 will be doing the examination for the government. 16 Dr. Brent, I'm going to ask you to raise 17 your right hand. 18 Whereupon, 19 JEFFREY BRENT 20 having been duly sworn, was called as a 21 witness and was examined and testified as follows: 22 SPECIAL MASTER HASTINGS: All right. Ms. 23 Renzi, when you're ready go ahead. 24 // 25 // Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 DIRECT EXAMINATION 2 BY MS. RENZI: 3 Q Good morning, Dr. Brent. 4 A Good morning, Ms. Renzi. 5 Q Could you please state your name for the 6 Court? 7 A Sure. It is Jeffrey Brent, B-R-E-N-T, M.D. 8 Q And what are your professional titles? 9 SPECIAL MASTER HASTINGS: Please speak up. 10 MS. RENZI: Okay. I will speak up. 11 BY MS. RENZI: 12 Q What are your professional titles? 13 A I am presently a full clinical Professor of 14 Pediatrics and Internal Medicine at the University of 15 Colorado Health Sciences Center in Denver. 16 Q And do you also maintain a private practice? 17 A Yes. I have a private practice which is a 18 group practice. It's a single specialty practice that 19 deals solely with issues related to medical 20 toxicology. The name of the practice is called 21 Toxicology Associates. 22 Q And could you briefly go through your 23 education and training? 24 A Okay. How far back do you want me to go? 25 Q Start with your undergraduate degree. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Okay. You may have listened to me long 2 enough to realize my undergraduate was obtained in New 3 York where I went to college and subsequent to that 4 did a Master's and subsequently a Ph.D. in 5 Biochemistry at the Mount Sinai School of Medicine in 6 New York. 7 Following that I went to Columbia University 8 College of Physicians and Surgeons as a postdoctoral 9 fellow there. After completion of my postdoctoral 10 fellowship I attended medical school at the State 11 University of New York School of Medicine at Buffalo, 12 New York, and then went to Harvard where I served as 13 an intern and subsequently ended up completing my 14 primary residency at Emory University School of 15 Medicine in Atlanta. 16 Once I graduated from that I moved to 17 Colorado to pursue a subspecialty fellowship in 18 medical toxicology. That was a two-year fellowship. 19 I did that fellowship from 1987 to 1989, and upon 20 completion of the fellowship I got offered a faculty 21 appointment to stay on. 22 It was a very attractive offer and I stayed 23 on, and I've remained basically in Denver on faculty 24 and in practice ever since. 25 Q Could you briefly list some of the honors Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 you have received? 2 A I could. I mean, you know, they're listed 3 on my curriculum vitae. I assume everybody has a 4 copy. I can give you one or two examples without 5 going into any detail. 6 It's interesting when you think of honors. 7 There are ones that are the most prestigious and there 8 are the ones that are the most important to you, and 9 they're not always the same. 10 For example, the one that to me is the most 11 important to me was when I was given the Excellence in 12 Teaching Award from the second year medical students. 13 Not a big thing in the world, but I was touched by 14 that. 15 Probably the most prestigious was last year 16 I received what's called the Louis Roche Award from 17 the European Association of Poison Control Centers and 18 Clinical Toxicologists. I guess it's the year before 19 last now. 20 They award the Louis Roche Award to one 21 person each year as an acknowledgement of their 22 contributions in the field, and associated with that I 23 had to go and give what they call a Louis Roche 24 lecture, which is a big lecture that is at a meeting. 25 That was in Berlin. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q Have you had occasion to deliver to 2 professional groups lectures on toxicology? 3 A Quite often, yes. That is something that I 4 do quite a bit. I get invited to lecture not 5 infrequently both in the United States and abroad. 6 I've given multiple lectures -- I think most 7 of them are listed in my curriculum vitae -- on 8 various aspects of toxicology, including mercury 9 toxicity. 10 Q And what professional organizations and 11 honorary societies are you a member of? 12 A A whole group of them. The American Academy 13 of Clinical Toxicology, the American College of 14 Medical Toxicology, the American Medical Association, 15 the American College of Occupational Environmental 16 Medicine, European associations. I think that's most 17 of them. There might be one or two others. 18 Q And do you currently serve as a peer 19 reviewer for any medical journals? 20 A Yes. Oh, yes. 21 Q Could you list a few? 22 A Sure. I end up spending a lot of time being 23 a peer reviewer. I'm senior editor of one journal, so 24 I obviously peer review quite a bit for that, and 25 that's for the journal called Clinical Toxicology. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Clinical Toxicology is the largest circulation peer 2 reviewed journal in the world devoted to clinical 3 toxicology. 4 I also routinely peer review for a number of 5 other toxicology journals plus general medical 6 journals. I review quite a bit for New England 7 Journal of Medicine, Journal of the American Medical 8 Association, some occupational medicine journals, 9 environmental medicine journals. 10 Q And you have published over 200 peer 11 reviewed articles relating to toxicology? Is that 12 correct? 13 A Well, my publication lists over 200 14 publications. That includes peer reviewed articles, 15 books, book chapters, letters, abstracts and so on, 16 reviews of various kinds. 17 Q Have you ever received funding from a 18 pharmaceutical company for a speaking engagement? 19 A I recall back it was in the vicinity -- 20 don't hold me to this year, but I think it was maybe 21 in the vicinity of 1991. It was shortly after I 22 finished my fellowship. 23 I gave a lecture for which a pharmaceutical 24 company paid me with an honorarium for giving that 25 lecture. I don't recall any subsequent to that. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q And have you ever received money from a 2 pharmaceutical company for research? 3 A Back once again in the early 1990s I had 4 some grants when I was a fellow. I had just passed my 5 fellowship. I had a very, very small grant from a 6 pharmaceutical company, which I had a couple of other 7 grants from pharmaceutical companies. 8 I have not taken a grant -- I have not taken 9 pharmaceutical company research money -- probably in 10 15 years. However, I was an investigator on an FDA 11 grant. The money came from the FDA for a clinical 12 trial of a new antidote. A pharmaceutical company was 13 sort of my partner in that grant. I was the principal 14 investigator, but they were on the grant as well. 15 Q And other than your testimony today, have 16 you ever testified as an expert witness in a legal 17 case? 18 A Yes, I have. 19 Q Approximately how many times? 20 A Oh, boy. I don't know. Since graduating 21 from my fellowship in 1989, several dozen times 22 usually. 23 Q Have you ever testified as an expert witness 24 on behalf of a pharmaceutical company? 25 A I have. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q Can you recall the circumstances? 2 A I probably have over the years at least a 3 half a dozen times. One on behalf of Pfizer 4 Pharmaceuticals with regard to a medication that 5 caused hepatotoxicity and has subsequently been taken 6 off the market called Rezulin. 7 I gave testimony once on behalf of Merck 8 Pharmaceuticals. Another example, I think probably 9 the most relevant example, is I gave testimony once in 10 a case where the allegation was autism induced by 11 thimerosal. 12 Q And do you recall the name of that case? 13 A Yes. That was the Easter case. 14 Q And were you an expert for the 15 pharmaceutical company or the defendant? For the 16 defendant pharmaceutical company? 17 A For the defendant, GlaxoSmithKline, yes. 18 Q And did you testify at a trial in that case? 19 A No. I testified at deposition in that case. 20 There was ultimately no trial because the case was 21 dismissed on the basis of a Daubert motion. 22 Q Have you ever testified as a legal expert on 23 behalf of a medical device company? 24 A Yes, I have. 25 Q Could you describe that, please? Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Sure. In the early 1990s I was chair of a 2 national panel which was assessing the issues of 3 potential health effects in terms of systemic disease 4 related to silicone breast implants. 5 There was a lot of concern about it at the 6 time, and we had concluded that the data was very 7 anecdotal and didn't support systemic effects. I 8 think subsequently everybody has come to that same 9 conclusion. 10 However, during that time period of the 11 1990s there was a good deal of litigation going on 12 regarding silicone breast implants, and manufacturers 13 came to me and said would you testify regarding your 14 work that you did on silicone breast implants. I said 15 I would, time permitting, and I testified in a number 16 of those trials over the 1990s. 17 Q I'd like to move on now to your experience. 18 Could you describe your position as a clinical 19 professor at the University of Colorado Health 20 Sciences Center? 21 A Right. My duties at the University of 22 Colorado Health Sciences Center involve three things. 23 It involves some patient care, it involves teaching, 24 and it involves maintaining my academic activities. 25 Those academic activities are reviewed annually. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 The teaching is both my direct teaching in 2 the medical school by way of lectures and other 3 similar forms of teaching and bedside teaching. We 4 have a service which is called the clinical 5 pharmacology and toxicology consultation service where 6 we do consultations regarding adverse effects, 7 toxicology consultations regarding adverse effects of 8 drugs or chemicals, adverse drug reactions, whatever, 9 on people in the hospital. 10 Those consultations, because it's a teaching 11 hospital, are generally primarily done by the group on 12 the toxicology service, which generally involves 13 probably about five or six people, including a medical 14 toxicology fellow in training, maybe one or two 15 residents, a couple of medical students. 16 They do the initial assessment and then I 17 round with the patients at the bedside with them and 18 go over their assessment, go over their examination 19 and see how it concurs with my examination, go over 20 the laboratories, and then we discuss a plan of what 21 to do next, what our impressions are, and then the 22 house staff usually writes up a consultation note, 23 which I generally co-sign. 24 Q And could you describe the nature of your 25 private practice? Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A My private practice is Toxicology 2 Associates, and at Toxicology Associates we have three 3 major missions and that is patient care, teaching and 4 research in the area of medical toxicology. 5 Our patient care component, we actually have 6 two components to the patient care component, an 7 inpatient and an outpatient one. Our inpatient 8 component involves admitting patients directly to our 9 hospital. They're generally admitted directly to us. 10 Most often our hospitalized patients are intensive 11 care unit patients. I do a good deal of intensive 12 care medicine. 13 These are patients who have been acutely 14 poisoned for one reason or another. It could be a 15 drug overdose. It could be a child with an accidental 16 poisoning. In Denver at this time of the year we 17 treat a lot of rattlesnake bites. A couple of months 18 from now it starts getting a little cooler. We start 19 treating a lot of black widow spider bites. In the 20 winter we treat a lot of carbon monoxide poisoning 21 from heating systems. 22 We have patients who have adverse drug 23 reactions that can make them very sick, so there's a 24 number of ways that patients can end up coming to our 25 toxicology service and being admitted to our inpatient Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 service. 2 We also have an outpatient service, a 3 clinic, and in the clinic we see patients who have 4 concerns about occupational or environmental 5 exposures. 6 We will sometimes follow up patients that 7 we've seen in the hospital, and we also do a good deal 8 of following workers who are exposed to hazardous 9 material in their work where OSHA mandates that these 10 workers get followed periodically and evaluated, so we 11 do a lot of that as well. 12 Q Have you ever treated a patient with mercury 13 toxicity? 14 A Quite a number of times. Yes, I have. 15 Q Could you describe some of the circumstances 16 in which you've treated a patient? 17 A Sure. Absolutely. 18 SPECIAL MASTER HASTINGS: Before we go into 19 that question, let me interrupt. 20 Just for the benefit of those who may just 21 be coming on line within the last few minutes to 22 listen in on the phone conferencing, I wanted to let 23 you know that right now we have the testimony of Dr. 24 Brent, an expert witness for the Respondent, a 25 toxicologist from the University of Colorado. We have Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 just gone through his credentials and background. 2 I wanted to let the folks know that we 3 finished with the testimony of Dr. Chadwick earlier. 4 I told you yesterday the best information we had at 5 that point was we would not be able to put Dr. 6 Chadwick's testimony -- Dr. Chadwick was the witness 7 who was going to be coming in by telephone. We 8 wouldn't be able to put him on the phone conferencing. 9 It turned out at a last minute breakthrough 10 here we were able to put Dr. Chadwick's testimony on 11 this morning. I apologize to anyone who tuned in 12 after that. He gave very brief testimony, about 15 to 13 20 minutes. That testimony will be available by 14 downloading the audio from our website or by viewing 15 the transcript on our website. 16 I apologize to those who missed that 17 testimony, but now we've got Dr. Brent testifying for 18 the government with Ms. Renzi questioning him. 19 Mr. Renzi, why don't you ask that last 20 question again? 21 BY MS. RENZI: 22 Q Could you describe some of the patients 23 you've treated with mercury toxicity? 24 A Well, mercury toxicity is distinctly unusual 25 to see, so most of the time when we see it it's a very Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 unusual circumstance. 2 I've seen some workers who were overexposed 3 to mercury. I have had a patient not too long ago who 4 was a dentist and bought a dental practice from 5 another dentist who was apparently rather sloppy and 6 had spilled mercury from fillings on the floor. It 7 was a rug floor, and apparently there was mercury in 8 the rug. 9 Now, what this dentist who was my patient 10 did -- it was a woman -- is she not only ran the 11 practice, but she would also clean it. She used the 12 vacuum cleaner on the rug. Never use a vacuum cleaner 13 on a mercury contaminated rug because it vaporizes all 14 the mercury. She developed a neurological syndrome 15 and was found to have very high levels of mercury. We 16 ended up chelating her. 17 I had a patient who we believe her husband 18 tried to kill her by putting large amounts of liquid 19 mercury in her study in an area where it wouldn't be 20 seen and allowing it to vaporize in the air. 21 Probably my most colorful patient was a 22 gentleman we took care of -- we actually published the 23 case -- about a year or so ago who had a form of 24 Munchausen syndrome where they like to make themselves 25 sick and get medical care. He injected mercury Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 intravenously, liquid mercury intravenously, and then 2 came to my hospital. 3 Q Have you ever treated or examined a child 4 diagnosed with autism? 5 A Oh, yes. 6 Q Under what circumstances? 7 SPECIAL MASTER HASTINGS: Do speak up, Ms. 8 Renzi. 9 THE WITNESS: Well, under a number of 10 circumstances. One is that autistic children, just 11 like any other child, can end up accidentally 12 overdosing, and in fact it's a little bit more common 13 in autism because they have a tendency towards pica. 14 They have a tendency to put lots of stuff in their 15 mouth. 16 So we have had patients on our service who 17 were autistic who had overdose on various things. It 18 happens occasionally. It's unusual, but we do see it 19 from time to time. 20 When all this stuff about mercury toxicity 21 and autism spectrum disorder found its way into the 22 blogosphere and websites we started to get a number of 23 calls from mothers primarily asking about and wanting 24 to know if their child should be chelated with a 25 mercury toxic. We've seen a number of those as well. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 BY MS. RENZI: 2 Q I want to move on to your opinions today. 3 Do you have an opinion whether Michelle Cedillo's 4 autism is causally related to the receipt of 5 thimerosal-containing vaccines in conjunction with an 6 MMR vaccine? 7 A Yes, I do have an opinion about that. 8 Q What is that? 9 A Well, I've looked at the medical records 10 quite extensively. I've reviewed the literature in a 11 great deal of detail, and I think it's clear there's 12 no relationship between thimerosal administration and 13 the development of autism or ASD. 14 Q And do you have an opinion whether it is 15 more likely than not that the thimerosal-containing 16 vaccines that Michelle Cedillo received caused 17 an immune suppression that was ongoing at the time she 18 received her MMR vaccine? 19 A There's absolutely no evidence that I saw 20 that would suggest that thimerosal in the doses 21 administered in vaccines would cause 22 immunosuppression. 23 Q Doctor, you discussed in your credentials 24 that you're a medical toxicologist. Could you just 25 describe medical toxicology and how that differs from Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 toxicology? 2 A Sure, I would be glad to. 3 SPECIAL MASTER HASTINGS: Now, we just got a 4 slide on the screen so let me interrupt again. 5 It looks like we've got a set of slides that 6 Dr. Brent is going to be showing, and we have a paper 7 copy of those slides so let's mark that paper copy as 8 Respondent's Trial Exhibit No. 17. 9 We've just put on the screen page 1 of that 10 presentation, so go ahead, Dr. Brent. 11 THE WITNESS: Sure. Well, it's important 12 before I tell you what a medical toxicologist is, it's 13 important to understand what a toxicologist is. 14 Toxicology is simply the science of the 15 adverse effects of chemical substances on living 16 systems. There's no formal requirement to being 17 called a toxicologist. Anybody can tell you I've 18 studied the stuff and therefore, you know, I'm a 19 toxicologist. 20 In contrast, the use of the term medical 21 toxicology is a specific term that has attached to it 22 a whole series of very formal and official 23 requirements, and that comes from the fact that in 24 medicine we have a number of specialties -- you know, 25 we have pediatrics, internal medicine, surgery, so on, Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 radiology -- and a number of subspecialties under 2 those specialties, and all of those, all of the 3 recognized specialties and subspecialties, are under 4 the purview of what's called the American Board of 5 Medical Specialties. 6 Medical toxicology is a subspecialty. It's 7 a recognized subspecialty by the American Board of 8 Medical Specialties, and therefore to call yourself a 9 medical toxicologist you have to complete their 10 requirements and get certified as a medical 11 toxicologist, much like if you were going to call 12 yourself a cardiologist or if you were going to call 13 yourself a thoracic surgeon. You know, you'd have 14 specific requirements you'd have to meet under ABMS. 15 For medical toxicology you have to complete 16 a primary residency in a clinical field. Following 17 that you do a two-year full-time medical toxicology 18 subspecialty fellowship in an accredited program after 19 which you are then eligible to take the medical 20 toxicology certifying examination, and if you 21 successfully complete that certifying examination then 22 you are certified as a subspecialty, a board certified 23 medical toxicologist. 24 BY MS. RENZI: 25 Q And you are one of approximately 250 board Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 certified medical toxicologists in the United States? 2 A Yes. It's fascinating. You know, as 3 interesting as this field is, there's a very small 4 number of us that are actually medical toxicologists. 5 About 250 I think, 260 certified ones in the United 6 States today. 7 Q Dr. Brent, is it your understanding of this 8 case that the receipt of thimerosal-containing 9 vaccines by Michelle Cedillo caused an 10 immunosuppression that was ongoing at the time she 11 received her MMR vaccine? 12 A No. I think there's no evidence to support 13 that. 14 Q Okay. We'll move on to Slide 2. What is 15 thimerosal? 16 A Thimerosal is a preservative. It was a 17 preservative that was in vaccines and still is in some 18 vaccines and other medications that are given to 19 patients. It's been widely used as a pharmaceutical 20 since the 1920s. 21 In 1931, Powell and Jamieson published a 22 major study, which for its time was a state-of-the-art 23 safety study, which established its safety based on 24 current standards, and it continued to be used. 25 Actually its use blossomed incredibly during Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 World War II because what happened during World War II 2 is the military surgeons learned that where there is 3 penetrating trauma associated with blood loss, i.e., 4 gunshot wounds, that there would be a significant 5 beneficial effect on outcome, saved lives, if the 6 blood volume that was lost from bleeding was 7 aggressively replaced with blood plasma. 8 The blood plasma was preserved with 9 thimerosal, a great deal of use of very, very large 10 quantities of thimerosal during that period, with 11 clearly an excellent safety profile. 12 Q And how is thimerosal different from ethyl 13 mercury? 14 A There's a very important difference between 15 thimerosal and ethyl mercury. 16 Q And we're on Slide 3 now. 17 A What you can see, if I may just switch 18 around here for a minute. I'll try to bring the mic 19 over. What you can see here on the screen is the 20 thimerosal molecule. Thimerosal is chemically ethyl 21 mercury thiosalicylate. 22 Now, here you see this Hg atom. That's a 23 mercury atom. You see it's right here in the middle 24 of the molecule. This part of the molecule to the 25 left is the thiosalicylate part of the molecule, and Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 this part to the right is the ethyl mercury part of 2 the molecule. 3 As soon as this gets into the body, this 4 bond, which is a relatively weak bond, breaks and 5 hence you end up simply with ethyl mercury as opposed 6 to the whole thimerosal molecule, so thimerosal 7 becomes ethyl mercury plus thiosalicylate. 8 There's probably even some disassociation of 9 this bond in the vial before it even gets to the body, 10 so clearly ethyl mercury is a very different molecule 11 from thimerosal. 12 Q Doctor, on page 3 of Dr. Aposhian's report, 13 and that's Petitioners' Exhibit 55, he states that it 14 is an enigma that thimerosal was included in childhood 15 vaccines, and I'll quote, "because there is no bona 16 fide evidence for either thimerosal's presumed 17 bacteriostatic activity or presumed safety." 18 Have you read that? 19 A Yes. Yes, I have read that. 20 Q There's also a footnote cited by Dr. 21 Aposhian that relies on two government rulings for 22 that statement, and I'd like to show those. 23 A Right. 24 Q The first one is a 1982 FDA ruling that's 47 25 Federal Register 436. Have you read this ruling? Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Well, actually, Ms. Renzi, it wasn't a 2 ruling. It was a notice of proposed rulemaking and 3 request for comments, and I have read it, yes. 4 MS. RENZI: And I also have passed out a 5 copy to the Court and to Petitioners' counsel of the 6 actual rulings cited by Dr. Aposhian. 7 SPECIAL MASTER HASTINGS: Right. 8 MS. RENZI: I think that would be Exhibit 9 18. 10 SPECIAL MASTER HASTINGS: Let's make that 11 Respondent's Trial Exhibit 18. 12 BY MS. RENZI: 13 Q I'm sorry, Dr. Brent. Please continue. 14 A Yes, I have read it, and what it was was an 15 assessment by an FDA panel of the use of a series of 16 mercurial compounds as over-the-counter sort of 17 disinfectants. 18 We probably all remember growing up that 19 we've had merthiolate put on our wounds. Thimerosal. 20 There were a whole series of these organic mercurial 21 disinfectants, and the panel that was assessing the 22 safety and efficacy of those disinfectants had 23 expressed three areas of concern. 24 One is that if you in an unregulated fashion 25 just pour all the stuff directly on a wound -- you Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 know, you buy it over the counter. You just pour it 2 on the wound. You can get a very high concentration 3 on the wound, and therefore you can get a 4 concentration that could be potentially tissue toxic. 5 The second concern was that wounds have 6 associated with them some blood and pus and so on, and 7 they cited data that shows that thimerosal loses its 8 efficacy as a bacteria static agent when it comes in 9 contact with pus and therefore may not be a good thing 10 to use on a wound. 11 The third concern they expressed was one of 12 potential allergy. 13 Q Is this proposed rule in any way relevant to 14 demonstrate the doses of thimerosal contained in 15 thimerosal-containing vaccines are unsafe? 16 A No. No. It just dealt with that unique 17 circumstance of putting it on. You're buying it over- 18 the-counter and just pouring it on wounds. 19 It had nothing to do with its potential use 20 as a preservative in vaccines where these various 21 concerns wouldn't apply. 22 Q And is it relevant to demonstrate that the 23 doses of thimerosal contained in thimerosal-containing 24 vaccines cause immunosuppression? 25 A No. There's nothing about that. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 MS. RENZI: The second ruling that Dr. 2 Aposhian refers to us 21 C.F.R. 310.545. We can pull 3 that up on the screen as Slide 4, and I've also passed 4 out the actual ruling to the Court and Petitioners' 5 counsel 6 SPECIAL MASTER HASTINGS: So let's mark that 7 as Respondent's Trial Exhibit No. 19. 8 BY MS. RENZI: 9 Q And are you familiar with this ruling? 10 A I am. 11 Q Could you describe it, please? 12 A Sure. Thimerosal, like so many substances 13 that have been sort of used for many, many, many years 14 since the FDA evolved, ended up being sort of 15 grandfathered in and was used, did not go through the 16 typical new drug application process which right now 17 is a very, very complex process that the FDA requires 18 of new drugs to certify that they're appropriately 19 safe and effective for use. 20 What they did is they listed here 21 approximately 700 substances that had been used 22 medicinally over the years and had just sort of ended 23 up going through this grandfather process of being 24 used without the FDA doing a formal assessment of 25 their safety. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Yes, thimerosal was on that list. A number 2 of interesting substances were on that list if you 3 look. For example, aspirin is on that list; 4 lidocaine, which you might get if you go to a dentist 5 and get an injection to numb your gums; honey in cough 6 syrup, in cough drops is on that list. I was very 7 disappointed to see caffeine was on the list. I maybe 8 wonder if I should give up Starbucks. 9 The calcium salts which we give now to women 10 particularly who have bone loss to prevent that from 11 happening; the iron salts that we give to treat iron 12 deficiency anemia, or pregnant women very often need 13 iron salt; codeine. Almost all the vitamins in your 14 daily vitamin pill are on that list. 15 We could go on quite a bit with what's on 16 that list. You'll find wheat germ on that list, 17 garlic and thimerosal. 18 Q Is this regulation in any way relevant to 19 demonstrate that the doses of thimerosal and 20 thimerosal-containing vaccine are unsafe? 21 A There's nothing in this regulation that says 22 that. 23 Q Or that they cause autism? 24 A No. There's nothing that says that. 25 Q As a medical toxicologist, how do you Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 determine whether a person's exposure to a certain 2 chemical has caused a particular outcome? 3 A Well, in medical toxicology we have a very 4 formal set of criteria that we go through to determine 5 when we see a patient whether a chemical to which the 6 patient was exposed may have caused the condition that 7 we're treating or that that patient has. 8 Although it's rather a complicated 9 formalism, it can be really boiled down to three very 10 basic and simple steps. 11 SPECIAL MASTER HASTINGS: We've got Slide 5 12 on the screen now? 13 MS. RENZI: Yes. 14 SPECIAL MASTER HASTINGS: Go ahead. 15 THE WITNESS: We just ask three simple 16 questions, and the first and very important one is 17 what was the patient exposed to. I have to know what 18 chemicals the patient was exposed to to know whether 19 that chemical caused the adverse effects. To what was 20 the patient exposed? 21 Then we ask the question can that exposure 22 to that chemical under any circumstance cause that 23 patient's disease. I put there, and I hope I've got 24 this right. I believe that's your legal concept of 25 general causation. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 If the answer is no, that this chemical is 2 not associated with that disease, then we really don't 3 have to look any further. If the answer is yes, 4 however, then the next question becomes did that 5 chemical in this particular patient under these 6 circumstances cause this disease. 7 In other words, did the patient get a 8 sufficient dose of the chemical under the right 9 circumstances that's been shown to be associated with 10 that disease, and I think you call that -- correct me 11 if I'm wrong -- specific causation. 12 We always tell students all you have to 13 remember is three words: what, can, did. That 14 embodies this formalism, which if you apply it it can 15 be a quite complex exercise, but this is essentially 16 the formalism that you have to go through to reach 17 conclusions about whether a chemical can cause a 18 disease in general and whether it may happen in a 19 particular patient. 20 BY MS. RENZI: 21 Q I'd like to move on now to in vitro studies. 22 Doctor, what is an in vitro study? We're going to 23 pull up Slide No. 6. 24 A We talk about two different kinds of 25 studies, and they are referred in the scientific Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 literature to in vitro studies and in vivo studies. 2 An in vivo study or an in life study is a study that 3 is done in an intact animal or an intact human being. 4 On the other hand, many scientific studies 5 are done in the laboratory where we might work with 6 just cells that are taken from an animal or cells that 7 are taken from a human being, grown typically in 8 what's called a petri dish, and treated in some way 9 under experimental conditions. That's an in vitro 10 study. That's an in vitro study. 11 Q And if a chemical causes an adverse reaction 12 in vitro can you extrapolate that the same results 13 will occur in a human? We'll turn to Slide 7. 14 A Absolutely not. I'd like to make a couple 15 of points. Actually, if we could go back to Slide 6 16 for a minute? 17 It's important to realize that when you have 18 some cells growing, and I'll show you some pictures of 19 this in a bit. When you have some cells growing in a 20 petri dish in the laboratory they are in such a 21 dramatically different environment than when they are 22 in a whole animal or a whole human that they become 23 highly susceptible to all kinds of perturbations and 24 to all kinds of insults that would really never happen 25 when all the defenses that are present in the intact Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 animal or the intact human are there. 2 Now we can go to the next slide. Let's 3 take, for example, so we don't get too abstract, let's 4 take mercurial compounds like ethyl mercury. If you 5 were to do an experiment where you just take some 6 cells from an animal and grow them in a petri dish and 7 then put ethyl mercury on them, that is completely 8 different from administering ethyl mercury to an 9 intact animal. 10 Because when the cells are in an intact 11 animal there are all kinds of protective systems that 12 the body has against foreign substances. In the case 13 of mercury compounds, for example, there's a protein 14 called metallothionein which binds and inactivates 15 mercury. There's glutathione which inactivates 16 mercury. There's cysteine which inactivates mercury. 17 There's a variety of other proteins to which mercury 18 binds and is inactivated. 19 If you look at the mercury, organic mercury 20 like ethyl mercury in the blood which is going out to 21 the tissues, almost all of it is in red blood cells. 22 Those red blood cells aren't present when you just put 23 the ethyl mercury on the cells. 24 So for that reason the cells become so 25 vulnerable and things that could kill cells in vitro Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 at very low levels are harmless in vivo. Water. If 2 you put too much water on the cells you will kill 3 them. 4 The in vitro environment is a highly 5 vulnerable environment. Cells are very susceptible in 6 ways that they would not be in vivo, so you can never 7 make the assumption that affects you see in vitro 8 occur in vivo. 9 I was here actually when Dr. Aposhian 10 testified about that, and he himself said if you just 11 show in vitro results nobody will believe that it 12 occurs unless you can show it in an intact animal. 13 Q And has the IOM commented on the use of in 14 vitro studies? 15 A As a matter of fact they have specifically 16 even in this context. We see here the 2004 IOM report 17 about thimerosal and vaccines, and it discusses the 18 various in vitro studies. 19 As you can see, they say, "Demonstration of 20 an adverse effect of mercury in vitro does not readily 21 translate into a physiologic argument." I think this 22 is a well accepted concept in science. 23 MS. RENZI: And that's Respondent's Exhibit 24 JJ at page 140. 25 SPECIAL MASTER HASTINGS: Thank you. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 BY MS. RENZI: 2 Q Are in vitro studies ever useful? 3 A Oh, yes. They're used all the time. 4 Q When are they useful? 5 A Well, they're useful in a number of 6 circumstances. Number one, they're useful for what we 7 call hypothesis generation. 8 If I want to know if a compound causes some 9 potential effect before I go to the very large expense 10 of an animal study, for example, I might want to see 11 what happens in vitro. If it doesn't do anything in 12 vitro it's not going to happen in the animal. 13 If I know there is an effect in a human, 14 let's say, or in an animal and I want to study what 15 happens on the subcellular level I can do that by 16 studying the cells in vitro, but you can never say 17 that's exactly what's happening in the animal, in the 18 animal or the human, until you test the animal or the 19 human. 20 Q Both Drs. Aposhian and Byers rely on in 21 vitro studies to form their opinions that thimerosal- 22 containing vaccines cause immune suppression. 23 Specifically they rely on two studies that 24 I'd like to discuss with you now. One is the Goth 25 study, which is Petitioners' Exhibit 55 at Q, and the Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 other one is the Agrawal study, which is Petitioners' 2 Exhibit 55 at Tab A. 3 In your opinion, is it reliable science to 4 extrapolate the results of these studies to conclude 5 that immunosuppression will occur in humans following 6 the receipt of thimerosal-containing vaccines? 7 A I think there's no reasonable way anybody 8 could conclude from the Goth and Agrawal studies that 9 the thimerosal from the vaccine would cause 10 immunosuppression. 11 Q We have the Goth study up on the screen as 12 Slide 8. Could you summarize the Goth study, please? 13 A Sure. It's an in vitro study, and it 14 studied a rare cell type in mice called the dendritic 15 cell. The dendritic cell plays a role in the 16 immunological response. They presented some data with 17 ethyl mercury and some data with thimerosal, but 18 really most of the meat of their experiments were done 19 with thimerosal. 20 Now, I'm not exactly sure why they did it 21 with thimerosal because if you'll recall cells in the 22 body are not exposed to thimerosal. They're exposed 23 to ethyl mercury following a thimerosal injection. 24 Thimerosal disassociates very quickly into ethyl 25 mercury. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 So they were looking at effects of 2 thimerosal, and we don't know to what extent, if any, 3 any of this translates into what would happen with 4 ethyl mercury. What they primarily studied were some 5 calcium influxes, which are part of the physiology of 6 these dendritic cells. 7 Q Dr. Aposhian testified that he found this 8 study compelling because the concentrations of 9 thimerosal that were used in this experiment was 10 almost equal to the concentration of thimerosal used 11 in thimerosal-containing vaccines. Is that correct? 12 A No. That is absolutely wrong. 13 Q Is the 100 nanomolars of thimerosal used in 14 the Goth study equivalent to the amount of thimerosal 15 that these cells would have been exposed to following 16 the administration of the thimerosal-containing 17 vaccine? 18 A Well, first of all you have to back up and 19 realize that following the administration of a 20 thimerosal-containing vaccine these cells would not be 21 exposed to any thimerosal at all. They would be 22 exposed to ethyl mercury, a different compound. 23 But let's put that part aside for a minute. 24 You know, we have to look at what the cells would 25 actually experience following the administration of Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 the vaccine, the dose that they would get. 2 Now, the Goth study reported effects of 3 about 100 nanomolars when thimerosal was in the medium 4 in which the cells were incubated. Forgetting for a 5 minute that in the blood there is no thimerosal, let's 6 just put that aside. That amount, however, would be 7 equivalent to a mercury concentration of about 20 8 micrograms per liter. We convert 100 nanomolars over 9 to 20 micrograms per liter. 10 Now, it's critically important to realize 11 that we're talking about here's an example of how 12 dramatically different an in vitro and an in vivo 13 study can be. In the body when the cells are exposed 14 to mercury for a cell to be exposed to mercury the 15 mercury has to be free and available to interact with 16 that cell. 17 Now let me show you. We go to the next 18 slide, the little diagram. 19 Q And this is Slide 10. 20 A Here we have an example. Here we have a 21 picture of how cells experience substances that are in 22 the blood, and what you can see is that we have the 23 blood vessel and the blood is in the blood vessel. 24 The blood contains two things. It contains plasma and 25 cells. So we have the plasma, and we're not showing Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 here red blood cells. 2 Now, here is the tissue. Tissues lie 3 outside of the blood vessels. So material from the 4 blood diffuses in and out of the tissues through these 5 little pores in the blood vessels, and if they're 6 small enough to get through these pores it will go 7 through and interact with the cells. This is, for 8 example, how cells would experience ethyl mercury if 9 they were exposed to ethyl mercury, if there's ethyl 10 mercury in the blood. 11 Now let's look at what happens when there's 12 ethyl mercury in the blood. We know -- 13 SPECIAL MASTER HASTINGS: Now we've gone to 14 Slide No. 11. 15 THE WITNESS: We know that for 16 organomercurials, greater than 90 percent of the 17 organomercurial is actually in the red blood cell. We 18 see here we have most of the mercury here in the red 19 blood cells. Ten percent would be in the plasma. 20 A lot of that 10 percent, by the way, and 21 I'm going to put this aside for a minute, but a lot of 22 that 10 percent would be bound to these proteins we 23 talked about, so the amount that's free and that can 24 get through these pores is probably a much smaller 25 percentage. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Let's just use that 10 percent figure worst 2 case scenario. So what we see of the total mercury in 3 the blood, only this fraction of less than 10 percent 4 is actually free to interact with the cells. 5 Thus, when the Goth study has a mercury 6 concentration of 20 micrograms per liter from the 7 thimerosal in the medium and so the cells were 8 directly exposed to 20 micrograms per liter, that's 9 equivalent to 20 micrograms per liter in the plasma. 10 In order to get 20 micrograms per liter in 11 the plasma, we need a whole blood level of 200 12 micrograms per liter because 90 percent of it is in 13 the red cells. Two hundred micrograms per liter is an 14 incredibly high blood level. Most people in this 15 country are walking around with blood mercury levels 16 less than five micrograms per liter. 17 If you look at the Pichichero data after 18 vaccination, total blood levels are one to 1.6 19 micrograms per liter, and here we have an exposure 20 essentially equivalent to 200 micrograms per liter. 21 BY MS. RENZI: 22 Q Is this study scientifically reliable to 23 determine what will happen in humans following the 24 receipt of the thimerosal-containing vaccine? 25 A No. No, of course not. First of all -- Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q And we're on Slide 12 now. 2 A First of all, they used thimerosal, and 3 these cells aren't even exposed to thimerosal in the 4 body. As we just saw, the concentrations that they 5 used were unrealistically high. You never get these 6 kinds of concentrations from vaccines. 7 It's also important to remember that let's 8 just put all that aside. Let's just put all that 9 aside and say yes, they used ethyl mercury. They used 10 reasonable doses. Let's even say that. This study 11 still says nothing about the duration of effect. 12 You would expect that any effects they saw 13 would happen while the ethyl mercury was there and 14 then would go away once the ethyl mercury was gone. I 15 mean, you wouldn't expect anything they reported to be 16 a long-lasting or clinically significant effect. 17 Now, I looked at Michelle Cedillo's medical 18 records. Just as an example of the case here, her 19 last thimerosal exposure was approximately nine months 20 prior to receiving her MMR. Now, thimerosal in the 21 blood has about a eight day half-life, so that 22 thimerosal within about a month is essentially gone or 23 five weeks essentially gone. 24 So this thimerosal could not possibly have 25 been exerting any kind of effect nine months hence Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 when she got her MMR vaccination. 2 Q Drs. Byers and Aposhian also rely on the 3 Agrawal study, and I'd like to go over that as well. 4 A Sure. 5 Q That's Slide No. 13. Could you describe the 6 Agrawal study? 7 A The Agrawal study was in many ways similar 8 to the Goth study. It also studied dendritic cells in 9 vitro, but these were human dendritic cells. They 10 too, like Goth, studied thimerosal, but not ethyl 11 mercury. 12 They found that at 50 nanomolars thimerosal 13 there was a shift in dendritic cell function towards 14 what we call a TH2 or a pro antibody production and 15 anti-inflammatory posture of the immune system. They 16 saw this at 50 nanomolars. They did not see this when 17 they went down to 10 nanomolars thimerosal. 18 Q And like with the Goth study, is the 50 19 nanomolars of thimerosal that was used in Agrawal 20 equivalent to the amount of thimerosal that these 21 types of cells would have been exposed to following 22 the administration of a thimerosal-containing vaccine? 23 A No. It's exactly the same thing. First of 24 all, they used thimerosal, and these cells would never 25 be exposed to thimerosal, but let's just put that Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 matter aside for a minute. 2 The simple math tells us that 50 nanomolars 3 of thimerosal is equivalent to a blood mercury level 4 of 10 micrograms per liter. Now, once again this is 5 not whole blood. There's no red cells, so it's all 6 pure 10 micrograms per liter in the medium, just like 7 10 micrograms per liter in the plasma. 8 In order to get the 10 micrograms per liter 9 in the plasma you'd have to get a whole blood mercury 10 level of 100 micrograms per liter or actually probably 11 more for any interaction at this level in the cells, 12 so clearly these cells were overdosed with thimerosal. 13 Q And is this study scientifically reliable to 14 extrapolate what will happen in humans following 15 receipt of a thimerosal-containing vaccine? 16 A No. That would be a tremendous leap of 17 faith. First of all, it's an in vitro study so you 18 can never conclude that this is what is going to 19 happen in humans for all the reasons that we talked 20 about. 21 Secondly, once again they exposed these 22 cells to ethyl mercury. That's not even the right 23 substance. 24 Q Do you mean thimerosal? 25 A Yes, to thimerosal. That's not even the Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 right substance. Thank you. 2 You know, additionally they studied 3 dendritic cells from normal individuals, not ones with 4 ASD. They did not study anything about the response 5 of these cells to measles virus. They did not study 6 anything, for that matter, about ASD. 7 Like the Goth study, there's no implications 8 in this study about any long-lasting effect so here, 9 for example, once again to take us back down to 10 reality to the case that we're discussing here, 11 there's no reason to think even if these results 12 applied that they would possibly be applicable at the 13 time that Michelle Cedillo received her MMR vaccine. 14 Q Are in vitro animal studies scientifically 15 appropriate to extrapolate what will happen in humans? 16 A No. You can never conclude from an animal 17 study that exactly the same thing will happen with 18 humans. You could never get a drug approved through 19 the FDA just on the basis of animal studies because if 20 you want to know what happens in humans you have to 21 study humans. 22 Animal studies once again are very good for 23 hypothesis generation to see what happens and to ask 24 the question does it happen in humans, but the 25 scientific landscape is too replete with examples Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 where results in animals, even primates, don't 2 translate into what happens in humans. 3 I put a couple of examples here, the famous 4 saccharin example that caused a great deal of stir a 5 number of years ago where rats were getting bladder 6 cancer from saccharin and there was great concern 7 because that was all the diabetics had to avoid sugar 8 at the time. It turns out that doesn't happen in 9 humans. There's no relationship. 10 You know, everybody here I'm sure in this 11 courtroom takes Tylenol from time to time. It's a 12 very safe drug. Just a very tiny dose of Tylenol, a 13 subtherapeutic dose of Tylenol, is actually lethal to 14 cats. 15 I could just go on forever about these 16 various examples, but I won't. The bottom line is you 17 can never infer human causation only by animal 18 studies. 19 Q And is there any evidence that thimerosal in 20 the doses contained in thimerosal-containing vaccines 21 adversely affect immunological function in humans? 22 A There's not a single study. I believe 23 there's already been testimony here from Dr. Aposhian 24 that there's not a single study that would suggest or 25 that demonstrates that the dose of thimerosal in Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 vaccine causes adverse effects on the immune system in 2 humans. 3 Q And is there any evidence that Michelle 4 Cedillo's immune system was adversely affected by 5 receipt of thimerosal-containing vaccines? 6 A No. If we go back to looking at the timing 7 of her vaccination, between the time of her last 8 thimerosal-containing vaccine before the MMR, the time 9 she received her MMR, that was the time period of 10 about nine months between March of 1995 when she got 11 vaccinated with a thimerosal-containing vaccine to 12 December when she got her MMR. 13 There's nothing in the medical records that 14 suggests that she was immunosuppressed, that she had 15 increased infections, doctor visits for infections 16 during that time period. There's no indication that 17 she was immunosuppressed, nor would you expect her to 18 be. 19 Q Doctor, I'd like to move on to dose. 20 A Okay. 21 Q As a medical toxicologist, is it possible to 22 assess the toxicity of a substance without considering 23 dose? 24 A No, absolutely not. Dose is the most 25 fundamental concept that we deal with as a medical Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 toxicologist. 2 I know there's been discussion about dose 3 here earlier. I was here for some of that discussion. 4 I think there may have been some confusion about the 5 importance of dose so I'd like to just say a couple of 6 words about this. 7 You know, this concept really goes back to 8 Paracelsus and the famous saying, "Poison is 9 everything. Nothing is without poison." The dosage 10 makes it either a poison or a remedy. He was actually 11 talking about mercury compound at the time. 12 SPECIAL MASTER HASTINGS: We're on Slide 19 13 now. Go ahead. 14 THE WITNESS: And as you see here on Slide 15 20, the bottom line we take from Paracelsus and is 16 still quoted in every toxicology textbook today as a 17 fundamental principle is that there is no such thing 18 as a poisonous substance. There are only poisonous 19 doses. 20 There is no substance that at low enough 21 doses will not hurt you, and there is no substance 22 that at high enough doses can be toxic. Water. I've 23 had patients die from water, from drinking too much 24 water. Psychogenic polydipsia it's called. 25 Almost any medication which can be very Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 beneficial at certain doses, if you get the high doses 2 obviously as a medical toxicologist I can tell you can 3 cause significant adverse effects. 4 We think of things like cyanide as being a 5 pretty dangerous molecule, but in fact the bad news is 6 that as we're sitting here today we are breathing in a 7 couple molecules of cyanide with every breath we take, 8 but it's such low doses that it absolutely can't hurt 9 you. The same is true of mercury or virtually any 10 other substance. 11 BY MS. RENZI: 12 Q And this principle is accepted by the 13 scientific community? Is that correct? 14 A This principle is accepted as the most 15 fundamental principle of toxicology by the scientific 16 community. 17 Here you have a book called Casarett & 18 Doull. This was a book, by the way, that was endorsed 19 by Dr. Aposhian. It's probably the most widely used 20 basic scientific text in the world, and if you just go 21 to one of the first chapters, Principles of 22 Toxicology, you see here that they point this out very 23 clearly. 24 "One could define a poison as any agent 25 capable of producing a deleterious response in a Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 biological system, seriously injuring function or 2 producing death. This is not, however, a useful 3 working definition for the very simple reason that 4 virtually every known chemical has the potential to 5 produce injury or death if it is present in a 6 sufficient amount. 7 "Paracelsus phrased this when he noted, 8 'What is there that is not a poison? All things are 9 poison, and nothing is without poison.' Solely the 10 dose determines that the thing is not a poison." 11 If you go further in that chapter, 12 Principles of Toxicology, you see once again this is 13 emphasized. "The characteristics of exposure and the 14 spectrum of effects come together in a correlative 15 relationship customarily referred to as the dose/ 16 response relationship. This relationship is the most 17 fundamental and pervasive concept in toxicology. 18 Indeed, an understanding of this relationship is 19 essential to the study of toxic materials." 20 Now, I know there's been testimony here that 21 dose is an outmoded concept, but I think that 22 testimony is probably incorrect in terms of the 23 mainstream thinking in toxicology. 24 SPECIAL MASTER HASTINGS: Now, for the 25 record here I note that Dr. Brent has just read a Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 couple excerpts from the toxicology textbook that he 2 mentioned in his slides and in his testimony. 3 You've given us a copy, a paper copy, of 4 those excerpts. Let's mark that as Respondent's Trial 5 Exhibit No. 20. 6 Go ahead, Ms. Renzi. 7 BY MS. RENZI: 8 Q Doctor, I know you have one more example of 9 the fundamental concept. 10 A Yes. Let me show you one more very 11 important example, and you'll see why it's an 12 important example in a minute. 13 This is a well respected text on toxicology 14 by Sullivan and Krieger, and I want to draw your 15 attention to the chapter called Principles of 16 Toxicology. 17 SPECIAL MASTER HASTINGS: So now this is 18 going to be page 3 of our Trial Exhibit No. 20. 19 THE WITNESS: And the senior author of that 20 chapter, as you notice there, is Dr. Glen Sipes. Let 21 me just point out what Dr. Sipes has to say about 22 dose. 23 "One of the most important concepts in 24 toxicology is the dose/response relationship. The 25 underlying premise is that any compound can be toxic Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 if it is encountered in large enough doses. No matter 2 what the compound's potency or how little compound is 3 necessary to produce an effect, its respected toxic 4 dose threshold must be surpassed to produce toxicity." 5 Now, that chapter was written, as you saw, 6 by Glen Sipes. Glen Sipes is Professor of Medicine in 7 the Department of Pharmacology at the University of 8 Arizona, which is Dr. Aposhian's institution, and is 9 actually head of Pharmacology and Toxicology there. 10 And, as a matter of fact, if you look at the 11 Sullivan book, John Sullivan, the senior editor of the 12 book, is a dean at the University of Arizona. 13 BY MS. RENZI: 14 Q To discuss more about those, Dr. Aposhian's 15 report contained several examples of mercury toxicity 16 in humans, and I'd like to pull up Slide 24. We have 17 a comparison chart. 18 Can any comparison be drawn from these case 19 reports about the toxicity of low doses of ethyl 20 mercury in thimerosal-containing vaccines? 21 A No. No, clearly not. It's a very profound 22 chart that I think makes the point clearly. These are 23 the cases that were cited by Dr. Aposhian in his 24 report where there was information about dose or 25 exposure. It's basically three papers, Opitz, Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Nierenberg and Fagan. 2 The Opitz paper, that was a totally 3 different kind of mercury. It dealt with elemental 4 mercury vapor, and, yes, there was toxicity. The 5 calculated blood level that this person has from that 6 exposure was almost 500,000 micrograms per liter. 7 Now, a typical blood level we see in the 8 United States is one, two, three, maybe five 9 micrograms per liter depending on how much seafood you 10 eat. It could be 10 if you're a big sushi eater. 11 This is almost 500,000 micrograms per liter, and it's 12 elemental mercury vapor. Clearly this has nothing to 13 do with very low dose exposures to thimerosal or ethyl 14 mercury. 15 The Nierenberg paper is a case report about 16 the chemistry professor at Dartmouth, which I think 17 everybody here has heard about. She was using a very 18 scary form of mercury that has nothing to do with 19 anything in this case called dimethyl mercury, and her 20 dose was over a million micrograms of mercury. A 21 million micrograms. Look at her blood level. Almost 22 150,000 micrograms per liter. 23 The next one that Dr. Aposhian cited was the 24 Fagan report where thimerosal at high concentrations 25 was repeatedly applied to an individual's what's Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 called amphalocele, part of the remnant of the 2 umbilical cord. We don't know the dose, but we know 3 the blood level, which gives an assessment of those, 4 and here too -- look at this -- over 1,000 micrograms 5 per liter. 6 Now, by contrast -- by contrast -- if we 7 look at the Pichichero data on vaccination where 8 individuals got up to 62.5 micrograms of mercury, this 9 gives blood levels in the one to 1.6 micrograms per 10 liter range. 11 Clearly here we're seeing that the dosage to 12 cause these adverse effects are overwhelmingly higher 13 than anything that can possibly occur related to 14 vaccination. 15 Q Dr. Brent, what are the different species of 16 mercury? 17 A There are certainly different species of 18 mercury. There are many different kinds of mercury, 19 and it's important to remember that they are all 20 toxicologically different. 21 Here we have another quote from that 22 Casarett & Doull book. It says, "No other metals 23 better illustrate the diversity of effect caused by 24 different chemical species than does mercury." That 25 is true. The different forms of mercury have very, Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 very different chemicals. 2 In fact, I think there's already been 3 testimony by Dr. Aposhian in that regard as well. I 4 believe he agreed with that. 5 Q And which type of mercury exposure has been 6 the most extensively studied by scientists? 7 A It depends on the timeframe that you're 8 talking about. In the past it was probably mercury 9 vapor and organic mercury because of industrial 10 exposures. More recently it's probably been methyl 11 mercury. 12 Q And why is that? 13 A The reason for that is because of the fact 14 that we all get significant exposures to methyl 15 mercury via our diet through seafood. As physicians 16 we're always telling our patients back off on the red 17 meat, eat more seafood, and yet seafood is the source 18 of methyl mercury. 19 So it's important to remember that when we 20 talk about mercury compounds they're all different. 21 There is the organic. We divide them into two major 22 categories, the organic and the inorganic. The 23 inorganic can be mercury vapor or mercury salts. 24 There are a number of different organic 25 mercuries. One of them is methyl mercury, which is Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 the kind that you'd find in seafood, and I think there 2 has been some discussion here about Minamata disease 3 where the fish in Minamata Bay in Japan became highly 4 contaminated because of industrial release, became 5 highly contaminated with methyl mercury. 6 The individuals that were eating off those 7 fish -- there were lots of fishermen families -- got 8 very, very high doses of methyl mercury, and that 9 caused the condition called Minamata's disease. It 10 primarily affected individuals who were in utero at 11 the time of the exposure. That's methyl mercury. 12 It's very important to remember that methyl 13 mercury is a different compound from ethyl mercury, 14 and here you see an example of the significance of the 15 difference between methyl mercury and ethyl mercury. 16 Why is methyl mercury called methyl mercury? 17 Let me point this out. Here you see the structure of 18 methyl mercury, and it is a carbon and three 19 hydrogens, and that is what we refer to chemically as 20 a methyl group, so it is a methyl group attached to a 21 mercury atom, so it is methyl mercury. 22 On the other hand, where we have a carbon 23 and three hydrogens and then a carbon and two 24 hydrogens, that's what we call an ethyl group. So we 25 have an ethyl group attached to a mercury atom. That Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 is what we call ethyl mercury. This can have 2 unbelievable consequences in terms of the differences 3 in the properties of the compound. 4 Let me show you an example that is virtually 5 identical. Here we see a methyl group, just like a 6 methyl mercury. A methyl group attached to an oxygen 7 hydrogen group. An oxygen hydrogen group is an 8 alcohol group, so this is methyl alcohol. 9 Here we see an ethyl group attached to an 10 alcohol group, so this is ethyl alcohol. Ethyl 11 alcohol is what is in spirits. Ethyl alcohol is what 12 is in beer or wine. Ethyl alcohol is probably what 13 everybody is going to go drink at the end of the day 14 today. 15 Methyl alcohol, on the other hand, instead 16 of having an ethyl group and just having a methyl 17 group, it is also referred to as methanol or wood 18 alcohol, which is one of the more dangerous substances 19 known to mankind. Just small sips of methanol can 20 kill you, and for those people who survive the serious 21 illness that you get from methanol, they will almost 22 uniformly end up blind. 23 You can see here that there is a huge 24 difference between a methyl group and an ethyl group 25 when it's attached to a molecule. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 SPECIAL MASTER HASTINGS: And he was just 2 looking at Slide No. 27. Go ahead. 3 BY MS. RENZI: 4 Q So is it scientifically valid then to use 5 the toxicological properties of methyl mercury 6 exposure to determine what the effects of ethyl 7 mercury exposure will be? 8 A Of course not. 9 Q I'd like to turn now to reference dose. Up 10 on the screen we're going to show Dr. Aposhian's slide 11 that showed how the doses of mercury that Michelle 12 Cedillo received through her thimerosal-containing 13 vaccines relate to the Environmental Protection 14 Agency's reference dose for methyl mercury. 15 SPECIAL MASTER HASTINGS: Was that Slide 39? 16 MS. RENZI: No. Actually it's not a slide. 17 SPECIAL MASTER HASTINGS: Okay. No? 18 MS. RENZI: It's Petitioners' Trial Exhibit 19 1, page 39. It's Dr. Aposhian's slide presentation at 20 page 39. 21 SPECIAL MASTER HASTINGS: Okay. 22 BY MS. RENZI: 23 Q What is a reference dose? 24 A Okay. A reference dose is, if you'd go to 25 the next slide -- Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q Let's go to Slide 28. 2 A Yes. A reference dose is a concept used by 3 the Environmental Protection Agency, the U.S. EPA, and 4 what it is is a designation for that dose of a 5 substance when averaged over a lifetime of use would 6 not be expected to cause an adverse effect, would be 7 safe. 8 Now, it's important to remember that there 9 is no reference dose for thimerosal, and there is no 10 reference dose for ethyl mercury. What we just saw 11 shown on Dr. Aposhian's slide, which he took the 12 reference to those from methyl mercury and applied it 13 to ethyl mercury. That can't be done. They are 14 different compounds. 15 There's no scientific basis for applying one 16 reference dose for one compound to a dose of a 17 different compound, although I should point out that 18 even if we accept the reference dose -- remember, the 19 reference dose, it's not a dose you can't ever exceed 20 on any given day. I mean, we could easily exceed it 21 every time we have a seafood meal. It is just over a 22 lifetime. It's just an average dose over a lifetime. 23 If you were to figure out Michelle Cedillo's 24 mercury exposure, unless she had some other unusual 25 exposures from other sources she would be under the Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 reference dose even at this point in her life. 2 Q A reference dose is not a threshold amount 3 above which toxicity will occur. Is that correct? 4 A No, it is clearly not a threshold amount 5 above which toxicity occurs. There is a big 6 difference between the reference dose and the dose in 7 which toxicity will occur, as I'll show you in a 8 minute. 9 It's also important to remember that Dr. 10 Aposhian, when you talk about the EPA reference dose 11 for methyl mercury, there are other agencies that have 12 reference dose like the FDA and the Centers for 13 Disease Control, and really those don't get exceeded 14 by vaccinations. It's very rare for that to happen. 15 But, it's important to remember that you 16 cannot apply the reference dose as a daily limit. It 17 is an average over a lifetime. You have expected 18 exceedences over the course of days. 19 Q What was the basis for the EPA's reference 20 dose regarding methyl mercury? We're on Slide 30. 21 A The EPA's reference dose for methyl mercury 22 is based on events that happened initially in Iraq a 23 number of years ago when there was methyl mercury 24 contamination of grain that people ate. 25 And then there was data from the Faroe Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Islands which more updated our database with regard to 2 methyl mercury and was used in the reference dose 3 analysis. It dealt with prenatal exposure. It was 4 based on prenatal exposure to methyl mercury and 5 effects that were found related to prenatal exposure. 6 Now, it's important to remember. Reference 7 dose has nothing to do with risk of autism or ASD or 8 immunosuppression. None of that is implicit in the 9 reference dose. 10 What the reference dose is based on, and now 11 they use the Faroe Islands study. What the reference 12 dose is based on is looking at prenatal exposure and 13 then as you follow children out in time they are 14 clinically normal children, but if you do sensitive 15 testing on them you can find subtle subclinical 16 deficits based in learning memory and language in 17 children who are otherwise clinically normal. That's 18 the basis for the reference dose. 19 Now, it's important to remember. You had 20 asked the question, Mr. Renzi, about whether exceeding 21 the reference dose means there's a threshold for 22 toxicity. It's important to remember it's clearly not 23 because the technique used by the EPA to determine 24 this reference dose is called benchmark method. 25 What they do is they look at the population. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 They look at the effects of the population and through 2 the benchmark method come to a conclusion about dose 3 that is very, very unlikely to affect anybody in that 4 population. 5 They take that dose, and then they take just 6 a safety back just to be on the safe side. Of course, 7 that's EPA's job. Just to be on the safe side we'll 8 drop it down another tenfold below that, and that's 9 where the reference dose comes in, so there's a big 10 safety margin implicit in the reference dose. 11 Q So if we go back to Dr. Aposhian's chart, 12 and I think you've already said this. Would the 13 amount of mercury contained in Michelle Cedillo's 14 thimerosal-containing vaccines cause her to exceed the 15 EPA reference dose? 16 A Well, as you can see on individual days, 17 yes, she has exceeded the reference dose. In fact, 18 over the period of time that she was being vaccinated 19 she exceeded the reference dose. 20 If you go out, however -- remember, this is 21 something you average over a lifetime. If you go out 22 over a period of time you find that, no, she would no 23 longer be over the reference dose. 24 Once again, remember the reference dose 25 isn't even about the ethyl mercury or the thimerosal Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 from vaccines. It's about methyl mercury, so it's not 2 even applicable. It's not even applicable in this 3 instance. 4 Q Dr. Aposhian stated in his testimony that 5 autistic children have a mercury efflux disorder. Are 6 you familiar with the term mercury efflux? 7 A I've heard the term. 8 Q What is it? We'll look at Slide 31. 9 A Well, it's this hypothetical disorder that 10 is based on the belief that children with ASD somehow 11 cannot properly excrete mercury and hence become 12 mercury toxic. They have adverse effects of mercury. 13 This efflux disorder hypothesis is really 14 based on two studies. It's based on a study of Amy 15 Holmes, and it's based on a study of Bradstreet and 16 the Geiers. 17 This study I know was discussed here. It's 18 important to note that much better studies from other 19 investigators could not replicate the results of 20 either the Holmes study or the Bradstreet/Geier study. 21 Q Could we go over the Holmes study, please? 22 We'll start with Slide 32. 23 A Okay. 24 Q If you could describe that study, please? 25 A What the Holmes study purported to do was to Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 measure hair levels of mercury in autistics and 2 compare them to normal controls. 3 Here you see the data summarized. If you 4 look at the autistics, the hair levels were reported 5 out at about 0.47 parts per million. If you look at 6 the normal control, the hair levels averaged about 3.6 7 parts per million. 8 They therefore saw this difference and 9 concluded, and this is the conclusion of their paper, 10 hair excretion patterns among autistic infants were 11 significantly reduced relative to control. 12 Now, if you look at this data you're 13 immediately struck by the fact that something must be 14 very, very wrong here because there's a very 15 excellent, huge study, a United States Government 16 funded study called the NHANES study, National Health 17 and Nutrition Exposure Survey, and what the NHANES 18 study did was went out and surveyed randomly many 19 people in the U.S. population, and among things that 20 they looked at were hair levels of mercury. 21 If you look at what you expect from the 22 NHANES study of hair levels of mercury in the U.S. 23 population in children, you see that the average is 24 about 0.22 parts per million, remarkably close to what 25 was reported in the Holmes study for the autistics. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 But if you look at the normal control, they 2 have very, very, very elevated hair levels. This 3 suggests that there is something clearly wrong with 4 this data in that their controls are so highly 5 nonrepresentative of the general population in the 6 United States, and that's what you would think the 7 controls would be. 8 Q Does this study provide a reliable 9 scientific basis to conclude that autistic children 10 are not able to excrete mercury? 11 A No, it doesn't for a number of reasons. 12 Number one, the data doesn't make any sense. The data 13 clearly had a problem that has not been addressed in 14 the study: Why the autistics have normal hair levels 15 and the controls have so very elevated hair levels. 16 Number two, this study studies hair. Hair 17 is not a significant excretory organ for mercury. We 18 don't get rid of our mercury through our hair. There 19 is some mercury that goes out in the hair, but that's 20 an insignificant mode of excretion. 21 Q And what is hair a measure of? If you were 22 to measure the mercury in hair, what is it a measure 23 of? 24 A It's a reflection of blood levels. So this 25 suggests if this data were true, which obviously Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 there's an unaddressed problem with this data, that 2 the autistics have lower blood levels than the 3 controls, but then again the controls have such 4 numbers you really can't reach any conclusions about 5 that. 6 Q You stated earlier that this Holmes study 7 has never been replicated. Is that correct? 8 A Well, people have tried. 9 Q And we're now on Slide 33. 10 A There have been two subsequent studies that 11 have shown no difference in hair mercury levels 12 between autistics and controls. Actually there's been 13 three, but one of them has not been published yet. 14 Kern studied a number of cases of autism or 15 ASD with controls and found that there was no 16 significant difference in the hair levels between the 17 two. 18 Ip from Taiwan did a similar study with 82 19 cases and 55 controls and once again demonstrated that 20 there was no significant difference. 21 So it appears that the Holmes study, 22 probably because of the very unusual data that it had 23 in it, cannot be replicated. 24 Q Dr. Aposhian also relied in his testimony on 25 an MIT study, which I believe is the Hu study, H-U. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Yes. 2 Q We filed this as Respondent's Exhibit L, Tab 3 27, and we'll discuss it at Slide 34. Could you 4 describe the Hu study? 5 A Sure. I was sitting here as this was 6 described as the study that verifies that the Holmes 7 study was right. Basically it was a study from MIT 8 from an analytical laboratory where they reported hair 9 mercury concentrations in three people that had 10 autistic spectrum disorder. 11 Now, two of those individuals were 12 undergoing what they called having been "under 13 treatment for heavy metal detoxification." That 14 usually means no seafood, probably a chelating agent. 15 Lo and behold, these two individuals had low mercury 16 levels. 17 There was a third individual, an autistic 18 individual, who was not undergoing detoxification, and 19 his hair mercury concentration was 0.4 parts per 20 million, exactly what you'd expect from the general 21 population. 22 Q So this study is not a reliable scientific 23 basis to conclude that autistics cannot excrete 24 mercury? 25 A No, of course not. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q In addition to the hair studies, Dr. 2 Aposhian relies on a chelation study published by Drs. 3 Bradstreet, Geier, et al., in the Journal of American 4 Physicians and Surgeons, and that's Petitioners' 5 Exhibit 55 at Tab E. Have you read this article? 6 A Yes, I have. 7 Q We're now on Slide 35. Could you describe 8 the Bradstreet/Geier study? 9 A Sure. What that study involved was taking a 10 number of individuals who were diagnosed with either 11 autism or pervasive developmental disorder and 12 comparing them with controls, and they gave them a 13 mercury chelator succimer, also known as DMSA, and 14 they measured their urine mercury output. 15 Now, the control in this study were 16 individuals who were brought to Dr. Bradstreet's 17 clinic because of concern about mercury toxicity, and 18 what you can see here is that following the 19 administration of the succimer when they measured the 20 urine mercury levels there was higher mercury 21 concentrations in the urine in the autism and PDD 22 group than in the control group. 23 Q On page 77 of that Bradstreet article 24 there's a chart that I want to pull up for you to look 25 at. It's on the left-hand side. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Right. This chart basically gives the whole 2 population they studied. They did it in two parts. 3 They studied the whole population, and then they 4 studied a group where the autistics were matched by 5 age and sex to the controls. 6 This is the whole population study, and, as 7 you can see, looking at this whole population you had 8 the higher mercury excretion in the cases than in the 9 controls, but if you look one of the things that is 10 striking about this result is that their ranges are so 11 huge from zero to 60 micrograms of creatinine in the 12 urine, zero to six in the control, with standard 13 deviations, which is a measure of the variance of the 14 result, how different the results are from individual 15 to individual. 16 There are standard deviations here that 17 exceed the actual values that they were looking at. 18 This is a huge amount of variance in the study. 19 Q What are some of the other reliability 20 problems with the Bradstreet study? We'll go to Slide 21 36. 22 A Oh, there's a number of them. There is the 23 fact that the study clearly had some confounding by 24 diet. The authors themselves acknowledge it, but 25 didn't do anything about it. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Remember, the individuals who made up the 2 control group were people that were brought to this 3 clinic because of a concern about mercury toxicity. I 4 can tell you, this is a population that avoids seafood 5 like crazy and so it's very likely that the control 6 population had relatively low urine mercury because 7 they were avoiding seafood. They did not control for 8 that fact. They could have controlled for it, but 9 they didn't. 10 As we saw, the ranges and the standard 11 deviations were huge. There was a large amount of 12 overlap between the values in the autistics and the 13 control population. 14 Another thing. I looked at those numbers, 15 and I said, you know, with those standard deviations 16 I'm surprised the result was statistically 17 significant. I spent a lot of time with their 18 statistical methodology, as did other people in my 19 office, and based on the statistical methodology that 20 they describe in their paper I could not come up with 21 a statistically significant result which they said 22 that they had. 23 Further, there was no assessment of 24 compliance with the chelation treatments. We don't 25 know if the control were taking the chelation Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 treatment as much as the autistics were. It's 2 possible that they weren't because they might have 3 been less motivated to take it. 4 Q We'll go on to Slide 38. 5 A If you look at the urine excretion of the 6 autistics of the PDD population, it's really not 7 terribly different than what you would expect to see 8 in the general population under conditions of 9 chelation. 10 It's also important to realize, remember, 11 what they did is they gave the chelating agent, and 12 they measured the urine after that. They came to the 13 conclusion that yes, the chelating agent mobilized all 14 this amount of mercury. 15 Well, they don't know that. I think Dr. 16 Aposhian was very clear about this in his testimony. 17 He's done a lot of chelation research. What you have 18 to do in any chelation study is you measure the 19 unchelated urine, you give the chelator, and then you 20 measure the chelated urine to know if the chelator is 21 mobilizing any mercury. 22 For some reason, and I don't know what that 23 is, they didn't get a nonchelated urine. All they did 24 is they gave the chelator and they measured the urine. 25 That is a major flaw in this study. They also did not Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 exclude people who had prior chelation, and there was 2 a high likelihood that some of these people had prior 3 chelation. 4 The other thing is the question is what does 5 it tell you anyway? It's important to remember that 6 chelation challenges don't really tell you anything 7 about body burden of mercury. Most mercury is stored 8 in the kidney, and when you give a chelating agent 9 basically what it does is it mostly removes the 10 mercury that's in the kidney, so it's a good 11 reflection of kidney mercury, but it doesn't really 12 tell you about body mercury. 13 This study was published in the Journal of 14 American Physicians and Surgeons, which is very much 15 of a fringe journal with lots of alternative agendas, 16 and it's not even indexed by the National Library of 17 Medicine. 18 I should point out that this study was 19 attempted to be replicated by a better study that was 20 published in a legitimate journal, and that study 21 could not replicate the results of the Bradstreet 22 study. 23 Q And that's the Soden, et al. clinical study? 24 A That's the Soden study where they gave DMSA 25 to children with autism and to normal controls that Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 were also coming to their clinic, and they found no 2 difference in the excretion of metals, including 3 mercury, following DMSA. 4 The conclusion of their paper, and they were 5 talking about that there was this hypothesis about a 6 novel mode of heavy metal toxicity in autistics based 7 on the Bradstreet paper, and they were saying in the 8 absence of a proven novel model of heavy metal 9 toxicity the proportion of autistic participants in 10 this study with DMSA provoked excretion results 11 demonstrate an excess chelatable body burden of 12 arsenic, cadmium, lead or mercury is zero. The 13 proportion is zero that had an excess chelatable body 14 burden. 15 SPECIAL MASTER HASTINGS: And that was on 16 Slide 39. Go ahead. 17 BY MS. RENZI: 18 Q Is mercury efflux a recognized diagnosis in 19 the medical community? 20 A No. 21 Q We're on Slide 40. 22 A Yes. I have yet to find any standard 23 medical textbook that describes this condition. 24 You know, for all research that we do in 25 toxicology and research, that we do in medicine and Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 billing and virtually everything we do in medicine, we 2 communicate, is done on the basis of what we call ICD 3 codes, International Classification of Diseases. 4 Everything we do, every diagnosis we give, 5 has to be given in the form of an ICD code. This is 6 done internationally. If you look, there is no ICD 7 code for a mercury efflux disorder. It doesn't exist. 8 It's not recognized. There is fundamentally no 9 scientific support for the hypothesis that the 10 kinetics of ethyl mercury are any different in 11 patients with ASD than anybody else suggesting an 12 efflux disorder. 13 I heard testimony when I was here where Dr. 14 Aposhian said well, yes, the problem with the 15 Pichichero study is that they didn't study autistic 16 children, and had they studied autistic children they 17 would have gotten very different results. 18 Well, in fact there's not one shred of 19 scientific evidence that suggests that autistic 20 children have any different kinetics of ethyl mercury 21 than anybody else. 22 Q Dr. Aposhian presented the hypothesis 23 regarding mercury efflux to the IOM in 2004. Are you 24 aware of that? 25 A Yes, I am. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Q And that's Respondent's Exhibit L at Tab 4. 2 What did the IOM conclude? 3 A The IOM basically rejected the efflux 4 hypothesis by concluding that they were rejecting the 5 entire concept of an association between thimerosal 6 and the development of autism or ASD. 7 In fact, when you look at the body 8 contradicting the Holmes and Bradstreet studies, which 9 are highly questionable studies, I think it makes the 10 efflux disorder hypothesis completely implausible. 11 Q I want to turn now to Dr. Aposhian's 12 hypothesis that there is a genetically susceptible 13 subpopulation to mercury in autistic spectrum 14 disorder. To your knowledge, is there any evidence 15 that supports this hypothesis? 16 A I have found none. 17 Q We're on Slide 42 now. 18 A I know the ASD population. I follow it on 19 the internet. It's a subject of interest to me. It's 20 intensively scrutinized. There has never been a 21 susceptible subpopulation to thimerosal in the ASD 22 population identified. 23 Now, what's interesting about this is that 24 in instances where there is a genetic component to 25 cause a susceptible population to a chemical -- for Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 example, Wilson's disease where people are very 2 sensitive to copper -- with relatively little looking 3 the gene was easily identified. There are many 4 examples in toxicology where specific genes are 5 identified with specific kinds of susceptibility. 6 The ASD population has been studied more 7 intensively than almost any other population I can 8 think of with regard to genetic susceptibility to a 9 chemical substance, and not a single one has been 10 identified. 11 It's also important to realize if this 12 hypothetical genetic susceptibility hypothesis were 13 true there certainly has been no evidence presented 14 that Michelle Cedillo has whatever genetic 15 susceptibility. 16 Q I want to go to the next slide, which is a 17 bell curve representing dose amount necessary to cause 18 a toxic response. Could you explain this curve? 19 A Yes. It's important to understand what the 20 normal bell curve is when you want to talk about a 21 genetic susceptibility or a susceptible population. 22 If we take any toxicologic response -- let's 23 say the amount of alcohol that's required to render 24 somebody unconscious -- it's not going to be exactly 25 the same for everybody. There's going to be a good Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 deal of variation. 2 If you look over the scope of the entire 3 population you find that it generally falls into sort 4 of a bell-shaped curve. Most people are going to be 5 kind of in this range, some people significantly less, 6 some people significantly more. You normally expect 7 to see that kind of variation within the general 8 population. 9 On the other hand, if you have a 10 hypersusceptible population to a substance and you 11 look at what happens then what you see is that you get 12 the bell-shaped curve for most of the population, but 13 then you can identify another population here where 14 you have this susceptible population. 15 This kind of demonstration has never been 16 done with regard to thimerosal or ethyl mercury and 17 autism. 18 Q Dr. Aposhian used the example of acrodynia, 19 Pink's disease, to demonstrate that there is a genetic 20 susceptibility to mercury toxicity, but he did so 21 without knowing the dose or mercury blood levels. Is 22 his reasoning valid? 23 A No, clearly not. 24 Q I want to turn to the next slide. If you 25 could just describe what Pink's disease is? Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 A Sure. Here on Slide 45 we have some of the 2 clinical characteristics of so-called Pink's disease 3 or acrodynia, which has a lot of clinical features. 4 There's bright reddening of the skin, and feet 5 photophobia, intense discomfort, multiple other 6 manifestations. I didn't want to list all the 7 manifestations. 8 The manifestations, by the way, of acrodynia 9 are extremely similar -- almost identical -- to the 10 manifestations that you see from an acute high dose 11 exposure to inorganic mercury. 12 By the way, it is not autism or ASD. It has 13 nothing to do with it. It was linked to the fact that 14 when there was an outbreak of this children were using 15 calomel, which is mercurous chloride, as a teething 16 powder and hence were getting overexposed to mercury. 17 Q And what do we know about the blood levels 18 in acrodynia cases? 19 A Well, it's important to remember that in the 20 acrodynia cases they were almost all due to inorganic 21 mercury. 22 I could only find one case in the English 23 language literature and peer reviewed studies that has 24 suggested a possibility of acrodynia from thimerosal 25 in one individual who got massive amounts of Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 thimerosal, so it's really all mercurous chloride. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 Mercurous chloride can be assays as what 2 comes out in the urine to measure urine levels and so 3 one of the things we know, and actually there is a 4 very interesting paper which I guess has recently come 5 up in this litigation. I hadn't seen this paper in a 6 while, but when it came up in this litigation I went 7 back and re-read it. It's truly a fascinating paper. 8 It demonstrates unambiguously that urine 9 mercury concentrations tend to be very high, 10 exceedingly high, in acrodynia, suggesting that 11 acrodynia is due to very high exposures to mercury, to 12 mercurous chloride. 13 Q And we'll bring up that article that you're 14 referring to. 15 A Right. This is basically reviewed. 16 Q Is this article the Court's exhibit that 17 we're referring to? It was given to me by the Court. 18 SPECIAL MASTER HASTINGS: It was given us by 19 what? 20 MS. RENZI: It was the article that was 21 given to Respondent by the Court. 22 SPECIAL MASTER HASTINGS: Go ahead. 23 THE WITNESS: This article was pointing out 24 that conventional wisdom had been some children get 25 acrodynia, and many do not, when using this teething Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 powder. 2 You know, the conventional wisdom, which has 3 really been carried on in a lot of the literature, is 4 that therefore it must represent some sort of an 5 idiosyncratic reaction. Some get it. Some don't. 6 But, as a matter of fact, it's probably due to the 7 fact that the ones who got it had very high exposures. 8 In this article, this Warkany article, 9 they're reviewing studies, and they point out when 10 they're talking about this study of Holzel and James 11 of 94 children with active acrodynia, in 61, or 65 12 percent, there are increased amounts of mercury 13 ranging from 200 to 2,500 micrograms per liter found. 14 Now, they're talking about urine here. Normal urine 15 mercury is maybe one or two micrograms per liter, so 16 this is a very, very high mercury level. 17 These authors state that no abnormal mercury 18 secretion was detected in 33, or 35 percent, of the 19 patients, but it is not clear how many excreted 20 significant amounts under 200 micrograms per liter, 21 and that's because the techniques that were in play at 22 the time when this was done could not get below about 23 200 micrograms per liter, so there could be 24 individuals in there with 100, 150, 180, huge mercury 25 levels, that make up the rest of that group. Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 BY MS. RENZI: 2 Q And finally, Doctor, has any agency or 3 scientific body ever concluded that there is a 4 relationship between the ethyl mercury contained in 5 thimerosal-containing vaccines and autism spectrum 6 disorder? 7 A No. You know, there are a number of 8 governmental agencies and mainstream nongovernmental 9 agencies who have taken the position that there is no 10 relationship. 11 That includes obviously the National Academy 12 of Sciences, the Institute of Medicine Panel, which 13 has rejected -- taken the unusual step of rejecting -- 14 the possibility of a relationship. The American 15 College of Medical Toxicology has taken the position 16 there's no relationship. The American Academy of 17 Pediatrics has said there's no demonstrable 18 relationship. 19 The World Health Organization has said 20 there's no demonstrable relationship. The U.S. CDC 21 has said there's no demonstrable relationship. The 22 European Medicines Agency, which oversees 23 pharmaceuticals in the European Union, has said 24 there's no relationship. 25 To answer your question, not a single such Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 organization has taken the position that there is a 2 relationship. 3 MS. RENZI: Thank you. I have no further 4 questions. 5 THE WITNESS: Thank you. 6 SPECIAL MASTER HASTINGS: And that was 7 looking at Slide 47. 8 MS. RENZI: Slide 47. 9 MR. MATANOSKI: Before we take a break, I'd 10 just like to clarify for the record. 11 The Warkany article, the 1953 article, I 12 believe that that was provided by one of the Court's 13 clerks to both parties approximately two or three days 14 ago. 15 SPECIAL MASTER HASTINGS: All right. Thank 16 you for clarifying that. 17 MR. MATANOSKI: Certainly. 18 SPECIAL MASTER HASTINGS: Let's take our 15 19 minute break at this point. 20 (Whereupon, a short recess was taken.) 21 SPECIAL MASTER HASTINGS: All right. We're 22 back from our morning break. 23 We have Dr. Brent back in the witness chair. 24 Ms. Chin-Caplan will have some questions for him. 25 Before we do that I just want to note Heritage Reporting Corporation (202) 628-4888


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BRENT - DIRECT 1 something very briefly for the record to clarify. 2 There was a reference during Dr. Brent's testimony to 3 an article called "Acrodynia and Mercury" by Dr. 4 Warkany and Dr. Hubbard. Ms. Renzi called this a 5 Court exhibit. 6 I just wanted to clarify for the record the 7 history on that. This article is about the 8 relationship between Pink's disease and mercury, a 9 topic that was raised in a number of the expert 10 reports filed in this case, particularly Dr. Aposhian 11 and Dr. Brent. 12 After Dr. Aposhian's testimony, he in his 13 testimony cited to a figure that one in 500 people was 14 considered to be susceptible to Pink's disease. We 15 had a question of where that came from. 16 We noticed in the Clarkson 2002 article, 17 which was filed both by the Petitioner as Exhibit 55, 18 Tab G, and by the Respondent as Exhibit L, Tab 13, in 19 that Clarkson article it made reference to this 20 Warkany article as the source of that number, so we 21 had our law clerk give copies of this article to both 22 sides and simply stated that there was interest in 23 this article and there might be a question about it 24 later in the proceeding. 25 We hadn't made it a Court exhibit, but we Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 will. We are going to at this time and file it into 2 the record so this article becomes a part of the 3 record in the case. 4 With that clarification, Ms. Chin-Caplan, 5 please go ahead. 6 MS. CHIN-CAPLAN: Thank you, Special Master. 7 CROSS-EXAMINATION 8 BY MS. CHIN-CAPLAN: 9 Q Dr. Brent, you indicated that you are 10 currently a clinical professor at Colorado Sciences 11 Health Center. Is that it? 12 A University of Colorado. Is this on? Can 13 everybody hear me? University of Colorado Health 14 Sciences Center, yes. 15 Q And you indicated that as a clinical 16 professor your duties and responsibilities are divided 17 into three areas. One was patient care, the second 18 was teaching, and I didn't catch the third one. 19 A Academic activities. 20 Q Academic activities. And when you say 21 academic activities, does that mean sitting on 22 committees and things like that for the hospital and 23 medical school? 24 A No. It means more scholarly activities -- 25 publications, research, a role in professional Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 organizations. 2 Q Okay. Now, approximately how much of that 3 time is spent in patient care? 4 A Are you talking about in my entire practice, 5 my private practice and the university? 6 Q Well, you said that you were a clinical 7 professor at University of Colorado. 8 A Yes. 9 Q I'm asking you how much of your time as a 10 clinical professor is spent in patient care? 11 A At the university? 12 Q Yes. 13 A Well, in my clinical professor role we see 14 patients at university and at Children's Hospital, 15 which are both part of the University of Colorado 16 system. 17 It depends on the year. It varies over 18 time. Right now I cover that service about two days a 19 month at the University of Colorado Health Sciences 20 Center, and I have about six days a month where I 21 cover the service at the Children's Hospital. 22 Q That's approximately eight days in the month 23 that you work as a clinical professor for the 24 University of Colorado? 25 A That I have responsibilities regarding Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 patient care consistent with my faculty appointment, 2 yes. 3 Q And would your teaching responsibilities be 4 included within that eight-day period? 5 A No. Well, I shouldn't say that. My bedside 6 teaching responsibilities are, yes, where we have 7 patients on the service that we round on and see as a 8 group and I supervise the care. But, no, I have other 9 teaching responsibilities beyond that. 10 Q And what are those other teaching 11 responsibilities? 12 A Well, you know, they vary quite a bit from 13 time to time. They are anything from months when it 14 can be one or two hours, or I've had months where I 15 have no hours of formal teaching responsibility other 16 than bedside teaching responsibilities, to I have had 17 months not long ago when I had six hours of formal 18 teaching responsibility. That includes, for example, 19 giving lectures to the medical school class. 20 There's been a little bit of a revolution in 21 the way medical education is carried out in the United 22 States right now. Traditionally it's been large 23 lecture hall classes. 24 It's making a transition now, which every 25 faculty member sets up, to a lot of small group Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 teaching and so, you know, we do spend a lot more time 2 now doing small group teaching. We'll have on some 3 subjects six or eight individuals that we'd be 4 teaching on a topic for a while. 5 Q So your teaching responsibilities can range 6 anywhere from zero to six hours a month? 7 A Yes. I can't remember a month where it's 8 been more than six hours. You know, once again 9 excluding bedside teaching. 10 Q And would that be primarily to medical 11 school students? 12 A Medical students, interns, residents and 13 fellows in training. 14 Q Okay. The clinical people -- the interns, 15 the residents and the fellows -- would those be the 16 people at the bedside? 17 A They would be both the people at the bedside 18 and in my formal lectures. 19 Q Okay. You indicated that your academic 20 activities take up part of your responsibilities. How 21 much time do you spend in academic activities at the 22 medical school? 23 A Well, my primary office is at my private 24 practice, so in terms of the actual academic 25 activities that I participate in -- for example, Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 teaching. Excuse me. For example, writing, editing 2 is done either in my medical office or in my home 3 study. 4 Q Private practice? 5 A Either in my medical private practice 6 office, or I do a great deal of my academic work, just 7 because of space considerations, in my home study. I 8 mean, I do a lot of my writing there, for example. 9 Q Okay. So where is your research done? 10 A It varies, depending upon the particular 11 project that I'm doing. 12 For example, right now my research involves 13 pesticide residues that are transmitted to individuals 14 through tobacco smoke, pesticides that are used to 15 grow the tobacco plant. We're doing that in 16 conjunction with people at the Colorado School of 17 Mines who have a very good assay system for these 18 pesticides. 19 Q The Colorado? 20 A School of Mines. 21 Q School of Mines. Is that an academic 22 institution? 23 A Oh, yes. It's a primarily Ph.D. granting 24 institution. 25 Q Okay. So your research is done at other Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 areas outside of the university? 2 A It depends on the project. It depends on 3 the project. I mean, I've done many projects within 4 the university. I've done many projects within my 5 private practice. 6 The work on these pesticide residues in 7 tobacco smoke is done in the lab that has the greatest 8 expertise to do these kinds of assays. 9 Q So you have no research laboratory at the 10 University of Colorado? 11 A I don't have my own research laboratory, no. 12 Q Okay. And you're working right now on 13 studying pesticide residues at the Colorado Safety & 14 Mines program? 15 A The School of Mines. The Colorado School of 16 Mines. It's a very, very internationally known 17 institution in scientific research. It is done in 18 conjunction with several hospitals and coroner's 19 offices. 20 Q So would it be fair to say that you're a 21 consultant with them? 22 A No. I'm an investigator. 23 Q You're an investigator? 24 A Yes. 25 Q Now, you also discussed your private Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 practice, and I believe it's called Toxicology 2 Associates? 3 A That's exactly right. 4 Q Doctor, how do you get patients referred to 5 you? 6 A Well, we do it in a number of ways. It's a 7 very interesting thing. Our practice is pretty well 8 known, and there aren't many toxicology practices 9 around so I think anybody from the Rocky Mountain area 10 who needs to refer somebody to a medical toxicologist 11 most likely will refer them to our practice. 12 We get patients coming down from Wyoming, 13 from Montana, from Utah, from New Mexico, from 14 Arizona, from Canada, from Nebraska. What happens is 15 we probably get half a dozen calls a day into our 16 office, and probably more, from people who call us and 17 they say I think I've been poisoned. We want to see a 18 toxicologist. 19 We have found that most of those kinds of 20 patients tend not really to benefit from seeing us 21 because they tend not to end up actually being 22 poisoned and there are other issues, so we have taken 23 the position, as in most specialty practices these 24 days, that for a patient to come to us they have to be 25 referred in from another physician so that some Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 initial screening is done to be sure it's appropriate 2 to send to a medical toxicologist. So our patients 3 basically come -- or a lot of our patients anyway come 4 -- through referrals from other physicians. 5 In addition, we have some various workers 6 that we follow in our worker surveillance program, and 7 of course our patients in the hospital, many of them 8 come to us directly through the emergency department 9 or get transferred in from other hospitals or 10 sometimes are in the hospital for another reason on 11 somebody else's service and ends up either it becoming 12 clear to them that they had an unrecognized 13 toxicologic problem and therefore were admitted 14 directly to us and then it became clear it was and we 15 get involved or that they've had a very bad adverse 16 drug reaction that requires consultation. 17 Q So with reference to your patient care, 18 would it be fair to state that it overlaps with your 19 hospital responsibilities? 20 A Oh, yes. The hospital responsibilities are 21 a very big part of patient care. 22 Q Okay. So that's in your private practice? 23 A Private practice and at the university. 24 Q And you get approximately half a dozen phone 25 calls, but most of your practice entails referrals Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 from other physicians? 2 A Yes. Yes. Right. We don't tend to see 3 patients on the basis of cold calls. 4 Q So in your private practice how much time is 5 spent on patient care? 6 A Oh, it varies. I would say, you know, 7 between the hospital work and the outpatient work I'd 8 say it's 30 or 40 percent of my time. 9 Q Now, you also indicated that you did 10 teaching in your private practice. 11 A Most of my teaching is associated with my 12 university work, although sometimes physically I'll be 13 giving lectures in my conference room to students and 14 so on. 15 Q So the students from the medical school 16 would come to your private practice office for 17 lectures? 18 A That's correct. It was on the toxicology 19 service, the specific toxicology service of which I'm 20 one of the attending physicians overseeing the 21 service. We give them a lot of lectures, the 22 individuals on that service. They rotate. 23 Sometimes we'll give them lectures at the 24 university hospital, the medical center. Sometimes 25 they'll come over to my office for lectures. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Sometimes they see patients with me in my office. 2 Q Since your teaching responsibilities at the 3 university are approximately zero to six hours per 4 month, does your private practice teaching encompass 5 that? Is it encompassed within that zero to six 6 hours? 7 A It is. 8 Q You indicated that you do research on 9 medical toxicology. You don't have a private 10 laboratory you indicated. Where do you get the topics 11 to research on? 12 A Well, a lot of it depends. You know, it 13 varies over the years. I spent many years doing 14 laboratory research. I published many papers on 15 laboratory research. 16 My interest is more clinical. I'm more of a 17 clinician. I like being around patients. I like 18 taking care of patients and so my research evolved 19 into a clinical trial research. That was that FDA- 20 sponsored research that I discussed before. 21 For a number of years recently we worked on 22 a number of major clinical trials. Ultimately we 23 published them in the New England Journal of Medicine. 24 They ended up getting some new antidotes approved 25 through the FDA, and now I am doing this tobacco work. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q I'm sorry? I missed that. 2 A And now I'm doing the tobacco work. 3 Q You indicated you're running a clinical 4 trial with FDA currently? 5 A No. I did. 6 Q You did? 7 A We're done with that now. We published it. 8 The drug is approved. We're done. 9 Q What was the drug? 10 A It's called Fomepizole. 11 Q And what is that for? 12 A Fomepizole is a drug. It's very 13 interesting. It's very interesting that you asked 14 that because as you'll recall, this morning we were 15 talking about methanol and how bad methanol was, 16 methyl alcohol. 17 Well, what's interesting about methanol is 18 that many people actually drink it, and we get a lot 19 of people come to the hospital that drink it. They 20 also drink a related substance called ethylene glycol, 21 which is an antifreeze. 22 These are potentially lethal things to 23 drink, and we developed a new antidote for the 24 treatment of methanol poisoning and for ethylene 25 glycol poisoning. The drugs's name is Fomepizole. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 It's marketed under the name Antizol. That's the 2 trade name. 3 We did clinical trials in both methanol 4 poisoning and in ethylene glycol poisoning that 5 resulted in the FDA approving the drug for both 6 indications. 7 Q Doctor, was that published in the Internet 8 Journal of Medical Toxicology? 9 A No. Both of those clinical trials were 10 published in the New England Journal of Medicine. 11 Q And was it also published in the Internet 12 Journal of Medical Toxicology? 13 A The clinical trials? No. 14 Q There's an article called, "Antidotes and 15 Alcohol: Has Fomepizole Made Ethanol an Obsolete 16 Therapy?" Is that the same topic that you speak of 17 for your clinical trial? 18 A That article relates to the clinical trials. 19 It's not the publication of the clinical trials. You 20 won't find the clinical trial data in that article. 21 Q And, Doctor, in that publication you 22 indicated that you received research support from is 23 it Orphan Medical? 24 A That's correct. 25 Q What is Orphan Medical? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Orphan Medical was my partner in the FDA 2 grant. It actually doesn't exist anymore, but it is a 3 company that specializes in the development of what is 4 called orphan drugs. 5 An orphan drug is a drug that is intended 6 for only a very limited use audience, and therefore 7 because of the small volume of people that intend to 8 use the drug major pharmaceutical companies generally 9 are not interested in developing these orphan drugs. 10 Orphan Medical's mission was to develop 11 these small, limited niche type of drugs that other 12 companies would not develop. Certainly this antidote 13 is an example of a drug, of a limited niche type of 14 drug, so they were very interested in developing that. 15 Q And what was their relationship to the 16 Fomepizole? 17 A Orphan and I had the FDA grant to develop 18 the drug, which is called an orphan drug grant. The 19 FDA has this program because once again it's important 20 to develop these orphan drugs, and since major 21 pharmaceutical companies don't have a big interest in 22 developing them the funds have to come from someplace. 23 The FDA developed this granting process and 24 so they were the company that was interested in 25 developing and subsequently marketing the drug. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q So did they provide the financial support 2 for this research? 3 A The support came through the FDA grant, and 4 it ran through Orphan. 5 Q It ran through Orphan? 6 A Right. 7 Q FDA granted fundings to a drug manufacturer 8 to fund research? 9 A Absolutely. This was the Orphan Drug 10 Development Grant Program, and it was specifically 11 intended to encourage the development of these 12 important orphan drugs. 13 Q But Fomepizole wasn't an orphan drug, was 14 it? 15 A Yes, it was. 16 Q Well, the title says "Has Fomepizole Made 17 Ethanol an Obsolete Therapy?" 18 A Right. 19 Q So ethanol was an existing therapy, correct? 20 A Yes. 21 Q So Fomepizole is not an orphan drug, is it? 22 A Well, there's two things about that. 23 Ethanol was used. It was never FDA approved for that 24 purpose, so it was not an approved drug for the 25 treatment of ethylene glycol and methanol poisoning. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Although it was used for that purpose, it did not have 2 FDA approval for it. 3 The second thing is there is nothing in the 4 orphan drug context that says if there is a therapy 5 for one of these sort of low niche diseases, low 6 population niche diseases, that you can't develop a 7 better therapy, and this is certainly a much better 8 therapy than ethanol therapy was. 9 Q But most of the orphan drugs don't have any 10 other therapies. Isn't that true? 11 A Well, I don't know about the other ones, but 12 I know that at least in this area where I was doing 13 research that although we did have a drug, ethanol, 14 Fomepizole was potentially and it turned out in fact 15 to be a very great improvement over ethanol, and the 16 FDA felt that they wanted to support the development 17 of Fomepizole through an orphan grant to us. 18 Q So that was your prior clinical trial. 19 Where were the clinical trials run? 20 A Where were the clinical trials? It was a 21 multicenter trial in a number of centers across the 22 country. I was the primary investigator that 23 coordinated the whole trial. 24 Q Okay. And how did they find you? 25 A Well, because I had an interest in the area Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 and in these particular poisonings. I had an interest 2 in the area of the poisonings. I had a very busy 3 clinical service where we saw a number of these 4 poisonings. 5 There was an investigator in Norway by the 6 name of Dr. Jacobsson who had done a lot of the basic 7 work in the development of the drug Fomepizole, and I 8 often contacted him just as a consultant to get some 9 information about how to proceed with the idea of 10 developing this drug. 11 Dr. Jacobsson could not be the primary 12 investigator. He was in Norway. He suggested that 13 they come and talk to me because I was very 14 knowledgeable in the area and I had a lot of 15 experience with these poisonings and I was a clinical 16 investigator. 17 Orphan called me and asked if I would be 18 interested in developing a clinical trial in this area 19 or two clinical trials actually. 20 Q So the individual whose research this really 21 was is in Norway and wanted to operate clinical trials 22 in the United States, and they needed a principal 23 investigator from the United States to coordinate 24 matters. Is that it? 25 A Well, no. Dr. Jacobsson had done a lot of Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 the basic preclinical research, had not done really 2 any studies on or had not done very much work on 3 individuals who were truly poisoned, but had done some 4 of what we call the preclinical research, done the 5 volunteers, showed it was safe, did some mechanistic 6 studies. 7 So the natural thing now would be to put the 8 drug actually in clinical trials. Clinical trials had 9 to be done in the United States because the FDA does 10 not like to accept drugs based on international data. 11 They really put strong pressure to do studies in the 12 United States. 13 Therefore, there was I think no question the 14 trial had to be done in the United States. I'm not 15 sure if it was even a requirement in our FDA grant 16 that it be done in the United States. It might have 17 been. 18 In talking to Dr. Jacobsson, they felt that 19 I was somebody for them to go to to discuss developing 20 this FDA grant and if we got it to develop the drug. 21 Q Do you know how it got from Dr. Jacobsson to 22 FDA? 23 A It didn't go from Dr. Jacobsson to FDA. 24 Q Then how did FDA become involved in this 25 grants process? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Orphan Medical was interested in the drug, 2 and they contacted Dr. Jacobsson in Norway to act as 3 kind of a consultant to help them make an assessment 4 about whether this would be a good drug to pursue, 5 whether this would be an improvement over existing 6 therapy. 7 Dr. Jacobsson I think encouraged them to go 8 through with the drug, felt very strongly that this 9 drug would be an improvement and ultimately 10 recommended that they contact me to do the clinical 11 trial. 12 Q But where does FDA fit into this? 13 A Orphan and I then went to the FDA and 14 solicited an orphan medical grant from the FDA to do 15 the trial. 16 Q So you went to FDA with the drug company to 17 solicit a grant from the drug company to do the 18 research? 19 A No. From the FDA to do the research. 20 Q But the FDA grant was funded by the drug 21 company? 22 A No. The FDA grant was funded by the FDA. 23 Q And Orphan had nothing to do with the grant 24 process? They didn't pay for any of this research? 25 A I think it all came from the FDA grant. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q Okay. Now, Doctor, we have your research, 2 this one piece of research that you discussed. What 3 else are you researching other than the research that 4 you're working with with the Colorado Mines? 5 A That's primarily it. I am very busy right 6 now. I'd like to be doing some additional research 7 projects, but in addition to the tobacco research that 8 we're doing I'm very busy right now with two other 9 issues. 10 One is my editorial responsibilities, and 11 the second is about three years ago we published a 12 major textbook in medical toxicology, and this was an 13 extremely time consuming, labor intensive activity. 14 It almost ruined my marriage. It ended up being a 15 very good book, and now we are getting prepared to go 16 into the second edition. 17 So I sort of have the next couple years of 18 my life scheduled in addition to various other 19 academic activities and professional society 20 activities and my research to doing the second edition 21 of the book, because it's about five years since the 22 first edition. 23 Q Do you have an active consulting practice? 24 A Consulting in what sense? We do lots of 25 different kinds of consulting. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q Do you consult to industry? 2 A We do from time to time, yes. 3 Q Do you consult to the drug companies? 4 A Occasionally. 5 Q Are you currently consulting with drug 6 companies? 7 A I'm not consulting with any drug companies 8 regarding any research areas or anything of that 9 nature. There are one or two medical/legal cases -- I 10 can think of one -- where I am looking at a case on 11 behalf of a drug company. 12 Q And what case is that? 13 A It's a case that involves an infant death 14 and any possible relationship to a diphenhydramine- 15 containing skin cream that was put on. 16 Q A what? I'm sorry. 17 A A skin cream that contained a medication 18 called diphenhydramine. 19 Q And you testified that you worked in the 20 Easter case, correct? 21 A I did work in the Easter case, yes. 22 Q And that was on behalf of the defendants. 23 Is that true? 24 A That's correct. 25 Q And the defendants were drug manufacturers? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A GlaxoSmithKline. I think there were some 2 others as well. 3 Q I missed that. 4 A GlaxoSmithKline was the company I was 5 working with most closely. I believe there were some 6 other defendants as well. 7 Q That was one of the drug manufacturers? 8 A That's correct. 9 Q How much did you get paid on that, Doctor? 10 A On the Easter case? 11 Q Yes. 12 A Oh, boy. I don't know the exact figure. I 13 had to go through all the records. It was a 14 substantial amount. I had to go through all the 15 records, actually went to Texas to participate in the 16 evaluation of the child, and then I had to prepare a 17 report, and I had a deposition in the case. 18 That was the end of the case. As I 19 mentioned, the case was dismissed on what's called a 20 Daubert motion, I believe. I'd be guessing, but it 21 could have been $40,000, $50,000. 22 Q Are you currently consulting on any other 23 thimerosal cases? 24 A No. I should say I have been sent on 25 occasion from pharmaceutical companies, to give a Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 complete answer, occasional thimerosal cases, but I 2 don't have any active ones going on, no. 3 Q Okay. And so in your medical/legal work 4 does it involve working solely for the defendants? 5 A No. 6 Q And in these cases that you've just 7 described to me have they involved working solely for 8 the defendants? 9 A The ones you've asked about where I've 10 worked as a consultant for the pharmaceutical 11 industry, yes, those have been for defendants. 12 Q Okay. Do you consult to Third World 13 countries at all? 14 A I have done some. It depends on what you 15 call a Third World country. 16 I don't have a lot of opportunity to do 17 that. I have done some things for emerging nations 18 through the U.S. State Department. 19 Q And what have you done for them? 20 A Well, one thing is really a fascinating 21 thing. It's a really fascinating thing. These really 22 weren't Third World countries, but they were sort of 23 emerging into mainstream countries, into mainstream 24 activities. One was China. One was Russia. 25 A number of years ago China invited a Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 delegation of medical toxicologists to come to China 2 to meet with their medical toxicology community, and I 3 was invited to lead that delegation. I was the 4 delegation leader and went there. 5 Then a really fascinating, an extraordinary 6 story in Russia. 7 Q Did you say in Russia? I'm sorry. 8 A In Russia. 9 Q What did you do in China? 10 A The delegation traveled and met with many of 11 their toxicologists or individuals who were interested 12 in toxicology, and we exchanged ideas and so on and 13 saw some patients together. 14 Q Okay. And you were moving on to Russia? 15 A Yes. It's a fascinating story, a 16 fascinating story. 17 I work with the United States Centers for 18 Disease Control in the rather scary area of chemical 19 weapons. 20 Q I'm sorry. I missed that. In the area of 21 what? 22 A Of chemical weapons because there's great 23 concern about what if there is a chemical weapons 24 attack, a terrorist attack. 25 They have harvested together a group of Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 about 12 medical toxicologists from around the country 2 to have a high level of expertise working on these, 3 being knowledgeable about them and to be able to 4 respond and take on leadership positions in case of an 5 actual event to get the knowledgeable people there on 6 the ground very quickly. I have a secret security 7 clearance with doing that. 8 Now, this is a very fascinating story. One 9 of the issues that came up was that the Soviet Union 10 used to have a very active chemical weapons program, 11 and with the dissolving of the Soviet Union there was 12 concern about what are all the chemical weapons 13 scientists doing. 14 The United States Government had a great 15 interest in, number one, finding out what they were 16 doing and, number two, figuring out ways to engage 17 them and so they send a number of medical 18 toxicologists to Russia to meet with the Soviet 19 weapons experts and to establish a dialogue and to 20 engage them and mostly to find out sort of what they 21 were doing in general. 22 We didn't interrogate them with what are you 23 doing, but just what they were doing in general and 24 what they wanted to be doing, the idea being that if 25 we could figure out what they wanted to do we might be Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 able to arrange funding for them to do it and to 2 prevent them from doing things that we didn't want 3 them to be doing. 4 That was a fascinating -- we did this two or 5 three years ago -- experience with the State 6 Department. 7 Q So this wasn't then at the invitation of 8 Russia? 9 A You know, I don't know exactly who 10 instigated it. I know what the agenda was from the 11 United States point of view, but I don't know who 12 instigated it. 13 Q Any other consulting to emerging countries? 14 A That's about all I can think of for now. 15 Q So there's nothing to Third World countries? 16 A No. No. 17 Q Any medical research in mercury? 18 A I published a number of papers on mercury 19 and have done academic assessments of the area. I 20 haven't done any primary research on mercury. I've 21 published a case or two on some treatment issues on 22 mercury. 23 Q Okay. So primarily on treatment issues? 24 A Yes. 25 Q So no primary research, but you have Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 published a few articles on how to treat mercury 2 toxicity. Is that it? 3 A Articles, book chapters. I've lectured 4 nationally and internationally on mercury toxicity and 5 a couple of publications regarding treatment. 6 Q Now, you indicated that you've actually 7 treated three mercury cases, correct? 8 A No. I've treated many, many more than three 9 mercury cases. I gave three examples. 10 Q Okay. One of the examples that you gave 11 were two workers who were overexposed to mercury on 12 the jobsite. Am I wrong? 13 A Today? 14 Q Yes. 15 A I remember giving the example of the 16 dentist. 17 Q The dentist. 18 A I remember giving the example of the woman 19 whose -- 20 Q Munchausen. 21 A -- husband was trying to kill her. 22 Q Right. 23 A Let me think. And the individual who 24 intravenously injected the mercury. 25 Q Who was the second one that you just Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 mentioned, the woman? 2 A Yes, who she thought her husband was trying 3 to kill her from the mercury. 4 Q Oh. 5 A I just chose off the board three colorful 6 examples, not the more mundane mercury cases. 7 Q So there was no situation where you were 8 consulted where two workers who were exposed to 9 mercury on the worksite? 10 A Oh, yes. I've seen a number of cases of 11 workers exposed to mercury on the worksite. I didn't 12 mention those examples today. They're not nearly as 13 colorful as the ones I mentioned. 14 I can't catalog every case of mercury 15 exposure that I've seen. I don't even think I 16 remember all the cases of mercury exposure that I've 17 seen. 18 Q So what are the industries that are still 19 using mercury on the worksite? 20 A That is a good question. You know, I don't 21 necessarily even know what the job processes are 22 because that's not necessarily part of my -- I 23 strictly do medical assessments of exposure and 24 medical condition. 25 But, I do know that in some industrial Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 thermometers they're still using a good deal of 2 mercury. Fluorescent bulb manufacturers are using 3 mercury. I'm sure there are others. 4 Q And have your cases come from those two 5 industries? 6 A I don't recall. Do you mean worker 7 exposure? 8 Q Yes. 9 A I don't recall specifically. 10 Q Now, I think you also mentioned that part of 11 your clinical responsibility is surveillance of 12 workers. Could you just describe what that involves? 13 A Oh, sure. I'd be glad to. OSHA has a 14 requirement that if workers are working in the area of 15 hazardous materials that they have to be in a medical 16 surveillance program, and that typically involves a 17 baseline evaluation before they start working and an 18 evaluation -- it can vary a little bit -- typically 19 once a year to assess them to assure that they are not 20 having any adverse effects from being exposed to 21 whatever the particular substances are. 22 Very often that often involves an assessment 23 of their ability to use an appropriate respirator as 24 personal protective equipment to prevent them from 25 inhaling material. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 There are a lot of workers that need to be 2 in these programs. We see a good number of them and 3 do their baseline evaluations. You know, if a worker 4 is going to go in working on a lead project they come 5 in and get their baseline evaluation just so we can 6 compare that with after they're finished working on it 7 or any other material. We see them annually. 8 We see them if they feel they've been 9 exposed, if something happened on the jobsite and they 10 feel they've been exposed. Sometimes if they really 11 are exposed we take care of them in the hospital, and 12 then often we'll see them at the termination of their 13 employment. 14 Q And how many programs are you currently 15 surveying? 16 A I don't know the number. 17 Q You don't remember? 18 A I have no idea. 19 Q Is it more than one? 20 A Oh, yes. 21 Q Is it more than 20? 22 A Probably, but I don't know. I can't tell 23 you for sure. 24 Q Do any of them involve mercury? 25 A I'm sorry? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q Any of them involve mercury? 2 A You know, it's possible because I know that 3 on some of the workers we've seen we've gotten mercury 4 levels, and usually what happens is our office -- not 5 me personally, but somebody in our office -- 6 determines in advance, because we have to let the 7 employers know how much it's going to cost, what tests 8 we're going to get and so the first thing that we ask 9 is what are the exposures, and then they can get the 10 appropriate tests. 11 I know I've seen a number of workers come 12 through where we have gotten mercury levels, so they 13 probably at least had the potential for being exposed 14 to mercury. 15 Q So when you order a screening do you order a 16 screening such as a heavy metal screening? Is that 17 it? 18 A No. Usually what we do is we order a very 19 specific test, not just a general heavy metal 20 screening, and it can vary depending upon the 21 circumstances. 22 For example, for mercury we can get either a 23 blood mercury level or a urine mercury level, 24 depending upon the circumstances. 25 Q So you would have to know ahead of time that Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 the person had already been exposed? 2 A Yes. 3 Q Now, Doctor, we discussed very briefly the 4 Federal Register, which you very kindly provided to 5 us. It's currently marked as Respondent's Trial 6 Exhibit 18. Doctor, this was proposed on January 5, 7 1982, is that correct? 8 A That is correct. 9 Q And the title of it is, "Mercury Containing 10 Drug Products for Topical Antimicrobial Over-the- 11 Counter Human Use: Establishment of a Monograph," 12 correct? 13 A That is correct. 14 Q And it was a proposed rule? 15 A That is correct. 16 Q The summary says, "The Food and Drug 17 Administration, FDA, is issuing an advance notice of 18 a proposed rulemaking that would classify over-the- 19 counter or OTC mercury-containing drug products for 20 topical antimicrobial use as not generally recognized 21 as safe and effective and as being misbranded." 22 Have I read that correctly? 23 A You have. 24 Q So, Doctor, as you indicated, thimerosal had 25 never been evaluated by FDA for safety and Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 efficaciousness, correct? 2 A That's right. It had been used for such a 3 long time with a good safety record that it just 4 continued to be being used without, to my knowledge, 5 an actual application for use, as was very common for 6 medications that had been around for a long time. 7 Q And it was grandfathered in, as you stated, 8 right? 9 A I believe that's the right term, yes. 10 Q Right. And there was a period of notice and 11 comment? Is that true? 12 A That's correct. 13 Q How long did it take for this law to become 14 effective? 15 A The rulemaking? 16 Q Yes. When did this law become effective? 17 A I don't know when it became effective. I 18 think it was a number of years later. 19 Q So the proposed rulemaking was first issued 20 on January 5, 1982, and the period of notice and 21 comment lasted until April 11, 2007, according to what 22 you handed out to us, correct, on Respondent's Trial 23 Exhibit No. 7? 24 A Let me take a look. What page? Written 25 comments by April 5, 1982. Reply by May 5, 1982. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Where are you talking about 2007? 2 Q Well, the effective date. It says April 11, 3 2007, doesn't it? 4 A What page are you looking on? 5 Q Respondent's Trial Exhibit No. 7, page 1. 6 MR. MATANOSKI: Just to clarify, I think 7 you're actually now looking at 21 C.F.R. � 310.545. 8 SPECIAL MASTER HASTINGS: That's 9 Respondent's Trial Exhibit 19. 10 MS. CHIN-CAPLAN: Is it 19? Okay. Exhibit 11 19. Sorry. 12 MR. MATANOSKI: And the notice of proposed 13 rulemaking is 47 Federal Register 436. 14 BY MS. CHIN-CAPLAN: 15 Q So, Doctor, the effective date was April 11, 16 2007? Am I correct? 17 A I think you may have changed years. I just 18 want to be sure I follow what's going on. 19 You had originally asked me about the 20 proposed rulemaking, and now we're not talking about 21 that anymore, but we're talking about -- 22 Q The rule. We're talking about the actual 23 rule. 24 A No, no, no. This rule did not derive from 25 this proposed rulemaking. These are two totally Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 separate areas. 2 Q They are? 3 A Yes. 4 Q And what is your knowledge about that? 5 A Well, the proposed rulemaking dealt with the 6 propriety of using mercury-containing over-the-counter 7 compounds in an unregulated way as an antiseptic for 8 skin, and that's what these comments were about, 9 strictly mercury-containing over-the-counter compounds 10 in an antiseptic for skin. 11 The 21 C.F.R. 310.545 was a list of about 12 700 compounds, substances -- not just mercury 13 compounds, but everything; everything from wheat germ 14 to vitamins -- that had been used by the FDA through 15 sort of this grandfather policy and had never gone 16 through the approval process that they were pointing 17 out. Thimerosal was one of those substances. 18 That's a totally different issue than this 19 proposed rulemaking on mercury-containing compounds on 20 skin. 21 Q So your belief is that 47 Federal Register 22 436 dealt solely with a topical -- 23 A Yes. 24 Q And, Doctor, 21 C.F.R. 310.545, which became 25 effective on April 11, 2007, involved thimerosal, Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 correct? 2 A Yes. 3 Q So FDA actually broadened the category of 4 mercury-containing products, didn't they? 5 A No. Actually I think you're mistaken. If 6 you look at this proposed rulemaking for topical, 7 there is a long list of mercury-containing products. 8 If you look at 21 C.F.R. 310.545, that has a 9 couple of mercury-containing products in it -- in 10 fact, I think much fewer than the proposed rulemaking 11 -- but is about 700 different pharmaceuticals 12 completely unrelated to mercury. Honey and wheat germ 13 and vitamins don't have anything to do with mercury. 14 Q You're absolutely right, Doctor, but the 15 proposed rulemaking that you have testified about you 16 indicate involved merthiolate, correct? 17 A Yes. 18 Q Which is a topical antiseptic applied to the 19 skin, correct? 20 A That is correct. 21 Q And the final rulemaking contained at 21 22 C.F.R. 310.545 involves all over-the-counter 23 thimerosal-containing products, doesn't it? 24 A It contains thimerosal, yes. Yes. It 25 includes thimerosal, over-the-counter or not over-the- Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 counter. 2 Q Correct. So hasn't FDA broadened their 3 category of mercury-containing products and there was 4 more than merthiolate that was being regulated in 21 5 C.F.R. 310.545? 6 A If you look at the proposed rulemaking, 7 there's a large list of mercury-containing products 8 here, more than merthiolate, in the original proposed 9 rulemaking. 10 Some of those products were carried on to 11 this other document, but most of the things on this 12 other document had nothing to do with mercury. 13 Q That's correct, Doctor. However, 14 merthiolate was just one kind of over-the-counter 15 product that contained mercury, wasn't it? 16 A That's correct. 17 Q And the final rule banned all thimerosal- 18 containing products over-the-counter, didn't it? 19 A Well, thimerosal is a merthiolate. 20 Q Yes. 21 A Yes. 22 Q But all of them. Anything that contained 23 thimerosal over-the-counter was banned, not just 24 merthiolate, wasn't it? 25 A Well, thimerosal was. This rule I don't Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 think is a banning rule. I mean, they didn't ban 2 aspirin. They didn't ban vitamins. They didn't ban 3 wheat germ. It just listed those products that hadn't 4 gone through the approval process. 5 Q So let's look at this law then, Doctor. 6 Under (a) it says, "A number of active ingredients..." 7 SPECIAL MASTER HASTINGS: Now you're looking 8 at page 1 of Trial Exhibit 19? 9 MS. CHIN-CAPLAN: Page 1. 10 SPECIAL MASTER HASTINGS: Okay. 11 BY MS. CHIN-CAPLAN: 12 Q Under (a) it says, "A number of active 13 ingredients have been present in OTC drug products for 14 various uses as described below. However, based on 15 evidence currently available there are inadequate data 16 to establish general recognition of the safety and 17 effectiveness of these ingredients for the specified 18 uses." 19 Thimerosal is listed as one of those 20 ingredients. Isn't that true? 21 A I think it's on this list. I can find it. 22 Let's see. 23 SPECIAL MASTER HASTINGS: Ms. Chin-Caplan, 24 it's a long list. 25 MS. CHIN-CAPLAN: Yes. I'm trying to find Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 the page for him. 2 SPECIAL MASTER VOWELL: It's on page 39, I 3 believe. 4 MS. CHIN-CAPLAN: Page 39? 5 SPECIAL MASTER VOWELL: Page 39. 6 MS. CHIN-CAPLAN: Thank you, Special Master. 7 SPECIAL MASTER VOWELL: At the bottom of the 8 page. Towards the bottom. 9 BY MS. CHIN-CAPLAN: 10 Q Page 39, Doctor. 11 A Okay. Now, on 39 are we still in (a)(1)? 12 Q Yes, we are. 13 A Okay. Actually, we're not. Page 17 becomes 14 (b). They go into bulk laxatives. 15 Q (a)(1). 16 A And then on page 18 they go into stimulant 17 laxatives, and then on page 19 they go into oral 18 health care products. We could go on and on, so I 19 think we're past that initial section by the time we 20 get to page 39. 21 Q Okay. Perhaps what we could do is get the 22 proper citation for the Court, so let's go through 23 this list here, Doctor, okay? 24 SPECIAL MASTER VOWELL: Ms. Chin-Caplan, in 25 the interest of time I believe rather than (a) it is Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 (i), but that may be indented so it means something 2 else. We're talking about first aid, antiseptic drug 3 products. 4 MS. CHIN-CAPLAN: Yes. 5 SPECIAL MASTER VOWELL: That is where 6 thimerosal is located. 7 MS. CHIN-CAPLAN: Thank you. Thank you, 8 Special Master. 9 BY MS. CHIN-CAPLAN: 10 Q So, Doctor, if you look immediately above it 11 on that page it looks like it is 27(i), and it starts 12 listing a number of mercury-containing products. 13 A Okay. So now we're going to page 39. Is 14 that correct? 15 Q Page 39. 16 A Okay. So here they are listing first aid 17 antiseptic drug products? 18 Q Right. 19 A Okay. 20 Q And they list a number of mercury-containing 21 products, correct? 22 A That is correct. 23 Q And underneath it there is mercury, correct? 24 A Correct. 25 Q And there is thimerosal? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A That's correct. 2 Q And merthiolate would be included within 3 this group of mercury-containing products, correct? 4 A That is correct. 5 Q But there is more than one mercury- 6 containing product here listed, isn't there? 7 A That's correct. 8 Q So hasn't FDA broadened its application of 9 the federal rule that they initially proposed in 1982 10 to include these other mercury-containing products? 11 A No. I think you missed the point. If you 12 look at the federal rule, there's a long list. 13 This proposed rulemaking, there's a long 14 list of mercury-containing products in here, a bigger 15 list than this, so I wouldn't describe it as 16 broadening. 17 Q Okay. Doctor, if we go to page 40, and the 18 citation there I believe would be 21 C.F.R. 19 310.545(b). Do you see where I am on page 40? 20 A I've got that. I'm looking for the (b). 21 Oh, the (b) on the bottom? 22 Q Yes. 23 A Yes. 24 Q It says, "Any over-the-counter drug product 25 that is labeled, represented or promoted for the uses Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 specified and containing any active ingredients as 2 specified in paragraph (a) of this section is regarded 3 as a new drug within the meaning of � 210(p) of the 4 Federal Food, Drug and Cosmetic Act for which an 5 approved new drug application under � 505 of the Act 6 and Part 314 of this chapter is required for 7 marketing. In the absence of an approved new drug 8 application, such product is also misbranded under � 9 502 of the Act." 10 I've read that correctly, haven't I? 11 A You have. 12 Q And, Doctor, while this was not an outright 13 ban, wasn't the practical effect of it a ban? 14 A You know, I don't know. You're asking me a 15 legal question, and you've certainly exceeded my legal 16 ability. I can tell you thimerosal is still used in 17 FDA approved pharmaceuticals. 18 Q That's right, in vaccines. 19 A And other stuff. 20 Q So, Doctor, in your report, and if I'm wrong 21 please tell me, you acknowledge that methyl mercury 22 has caused problems and Minamata Bay would be one of 23 those instances. Wouldn't that be true? 24 A That is correct. 25 Q And do you acknowledge, also, that methyl Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 mercury has caused problems in the Iraqi grain 2 contamination cases? 3 A It has. 4 Q And there were a number of those, correct? 5 A Yes. 6 Q And the Faroe Islands, that also looked at 7 methyl mercury, correct? 8 A Faroe Islands looked at methyl mercury. 9 Faroe Islands' data is a little complicated because of 10 the coingestion of polychlorinated biphenyl in high 11 concentrations that happens. We don't see those 12 polychlorinated biphenyls in the Seychelles Islands 13 and they don't see the same effects really in the 14 Seychelles Islands, so we don't know what to make of 15 the Faroe versus Seychelles dilemma. It's still an 16 unresolved question. 17 Q So are you aware of any literature that has 18 actually looked at the PCBs that were involved in 19 Faroe Islands and made a determination that it did not 20 affect the outcome of the study? 21 A They have attempted to control the PCBs and 22 concluded that they could not find evidence that the 23 PCBs were the cause of the difference. That has not 24 ruled out the PCBs certainly, but they could not find 25 evidence that the PCBs were causing the problem. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q You mentioned the Seychelles Islands. The 2 Seychelles Islands was also a seafood population 3 people, group? 4 A Seafood eating population, yes. 5 Q And to be perfectly clear the Faroe Islands 6 involved the ingestion of pilot whale, didn't it? 7 A That's correct, and that's where the PCBs 8 came from. 9 Q Right. And it was not a steady state of 10 ingestion, correct? 11 A That's correct. 12 Q And the Seychelles Islands involved a steady 13 state, correct? 14 A That's correct. 15 Q Now, you were present in the Court when Dr. 16 Aposhian testified, weren't you? 17 A I was here, yes. 18 Q Did you hear him say that when the White 19 House conference was convened of which he was a member 20 they were there to try and resolve this issue of the 21 Seychelles Islands with their steady state exposure 22 and the Faroe Islands with their bolus type of 23 exposures, correct? 24 A Yes. 25 Q Did you also hear what Dr. Aposhian Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 indicated occurred at that meeting? 2 A You'd have to tell me what specific aspect 3 of his testimony you're referring to. 4 Q Do you recall him saying that the 5 recommendation of this White House conference on 6 mercury was that the Seychelles Islands should utilize 7 the same tests as those utilized by the Faroe Islands? 8 A Well, yeah. There was definitely the issue, 9 and this has been well written about in the 10 literature, that there was not exactly the same 11 testing protocol between the Faroe Islands and the 12 Seychelles group. There was concern that may be why 13 they see effects in the Faroes and they don't see it 14 in the Seychelles. The suggestion had been made, 15 well, let's just do exactly the same test on both 16 groups. 17 The fact is that if you look at the testing 18 protocols they tested pretty much the same domains, 19 the same aspects of neuropsychological function and 20 neurocognitive function, they just used slightly 21 different tests to do it. 22 So there was certainly a question of well, 23 that may be the source of the discrepancy, but I think 24 there is considerable doubt in peoples' minds that 25 it's simply a result of the testing protocol given the Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 fact that the domains that they look at are so 2 overlapping between the two studies. 3 Q Do you recall Dr. Aposhian saying that when 4 they did utilize the same tests as the Faroe Islands 5 that they obtained the same results? 6 A I think you have to look very closely at 7 that. The adverse effects in the Seychelles that they 8 ultimately found were on a test called the grooved 9 pegboard, and that was one test on a large testing 10 battery. 11 It's unclear whether that one result on that 12 one test, and it was primarily seen with the 13 nondominant hand, which is strange, so it was 14 questionable whether that actually -- and the 15 literature reflects this. 16 It's not in my opinion, it's well-written in 17 the literature. The literature reflects that nobody 18 really knows what the significance is. I mean, you 19 know, it tested a little bit more abnormally on the 20 grooved pegboard test. They then did subsequent 21 analyses because -- and I don't want to get too 22 complicated about this, and stop me if I get too 23 complicated -- all these tests had been done using a 24 so-called linear model. 25 In other words, looking for a dose response Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 whereby, you know, you double the dose you expect to 2 see double the effect or some proportionate effect to 3 dose, and they couldn't find any effect on the grooved 4 pegboard on the dominant hand. They then went back 5 and they said well, let's try a different model, and 6 so they used what they call a nonlinear model. 7 We're saying well, let's assume it's not a 8 discognitive dose response group, let's assume it gets 9 flat, flat, flat, flat, flat and you reach a threshold 10 and it goes up. Using the nonlinear model they were 11 able to say, well, maybe there's an effect here on the 12 dominant hand. That's a lot of data dredging, and as 13 reflected in the publications nobody really knows what 14 the significance is. 15 Nobody knows whether you're supposed to use 16 a linear or a nonlinear model. So, yes, they found a 17 test, one test, where there was an abnormality in the 18 Seychelles that they saw in the Faroe Islands at an 19 older age group with lots of other confounding 20 factors. What that ultimately means in the long run, 21 I think the dust has to settle on that. 22 Q There was also a New Zealand study done as 23 well, wasn't there? 24 A Well, there was. There was a study by a guy 25 by the name of Karrollstan, with a K, in New Zealand, Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 and they did some analysis, too. That study has never 2 been published in the peer-reviewed literature, but 3 there was a study, which actually, as best as we can 4 tell given the study has never been published has 5 reported results similar to the Faroes. 6 Q Now, Doctor, the Iraqi grain cases contained 7 contamination with thimerosal as well, too, didn't 8 they? 9 A No. 10 Q Or ethyl mercury? 11 A Well, no. 12 Q There haven't been? 13 A There have been Iraqi grain cases where 14 there's miscontamination with ethyl mercury, 15 paratoluene sulfonates, if that's what you're 16 referring to. 17 Q Yes. 18 A EMPTS. EMPTS is not ethyl mercury, although 19 it's got a ethyl mercury in the name. It is a 20 significantly more complicated molecule than ethyl 21 mercury. 22 Q So it's your testimony that none of the 23 Iraqi grain contamination cases involved ethyl 24 mercury? 25 A I don't recall. I know there has been Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 methyl mercury, I know there's been EMPTS. I don't 2 recall if there was another one with ethyl mercury. 3 Q Okay. Now, Doctor, in addition to the grain 4 contamination cases there have been a number of ethyl 5 mercury poisonings, haven't there? 6 A Yes, there have. 7 Q And you actually listed quite a few of them 8 in your report, didn't you? 9 A Yes. In my report? 10 Q Yes. 11 A Yes, I mentioned some. Yes. 12 Q Before we move on to that area, Doctor, do 13 you recall Dr. Aposhian saying that at the end of this 14 White House conference of which he was a member that 15 the FDA agreed to lower their standard to meet that of 16 EPA? 17 A He might have said that. I don't recall. 18 Q Okay. Now, on page 15 of your report you 19 say there is reliable scientific evidence that 20 thimerosal is not toxic to humans including infants 21 and children at doses delivered either individually or 22 cumulative by thimerosal containing vaccine, and on 23 page 16 you list a number of cases. I'd like to go 24 through those cases with you. The first one that I 25 see was the Stajich article. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Uh-huh. 2 Q Stajich is contained at Respondent's 3 Exhibit L, Tab 54. Do you have that, Doctor? 4 A I don't have that article. I might have it 5 here on my computer. You have a hard copy of it? 6 Okay. 7 Q Okay. This involved mercury exposure after 8 hepatitis B vaccination in preterm infants, correct? 9 A I believe it was term and preterm infants. 10 Q Okay. They compared pre and postvaccination 11 mercury levels. Is that true? 12 A Yes. 13 Q And they indicated in the abstract that it 14 showed a significant increase in both preterm and term 15 infants after vaccination, correct? 16 A Sure. 17 Q Then they said that additionally 18 postvaccination mercury levels were significantly 19 higher in preterm infants as compared to term infants, 20 yes? 21 A Sure. 22 Q Then it says because mercury is known to be 23 a potential neurotoxin to infants further study of its 24 pharmacodynamics is warranted. I've read that 25 correctly? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Yes. 2 Q You don't disagree with that, though, do 3 you? 4 A Well, once again, you know, I spent a lot of 5 time this morning talking about dose. Yes, there's no 6 question in my mind that at a high enough dose that 7 mercury is a neurotoxin to infants and to adults. I 8 think what we're showing here is if you look at these 9 levels that these levels are certainly not anything 10 close to what you would expect to be associated with 11 any toxic effects. 12 Q Doctor, I'd like you to take a look at the 13 Haeney report, which is contained at Respondent's 14 Exhibit L, Tab 23. Could you just tell the Court what 15 this case involved? 16 A Sure. I just want to see if I have it on my 17 computer. I'll take a look at it here in a second for 18 you. Okay. This one I believe is the study where 19 they gave long-term administration of infants who had 20 a condition known as hypogammaglobulinoemia, they had 21 decreased immunoglobulin levels, and so they infused 22 them with immunoglobulins. 23 Q I'm sorry. Did you say infants? 24 A Patients. I'm sorry. Patients. 25 Q And what were their ages? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Let's see what their ages were. 2 Q It's at the top of page 13. 3 A Let's see. Twenty-six patients, four to 67. 4 Q Yes. 5 A And so they infused them with immunoglobulin 6 containing thimerosal and fundamentally these people 7 obviously developed elevations in their blood mercury 8 level because of the thimerosal, but it was basically 9 well-tolerated. Mercury levels went much, much higher 10 than anything you would see with vaccinations. 11 Q Doctor, on page 14, the very last sentence, 12 doesn't it say hence, most patients with 13 hypogammaglobulinemia are theoretically at risk for 14 mercury exposure, and although no clinical evidence of 15 toxicity is yet apparent physicians responsible for 16 each patient must be alert to the need for continued 17 long-term detailed clinical examination to detect any 18 subtle disturbances that may occur? I've read that 19 correctly, right? 20 A You've read that correctly. Basically, what 21 they're saying here is look, we have given this 22 immunoglobulin to all these people, and we have driven 23 mercury levels up very high, very high, and yet we do 24 not see clinical toxicity. They haven't driven it up 25 high enough to get clinical toxicity, but they're huge Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 compared to what you'd get from a vaccine. 2 So, yeah, I think they're saying look, we 3 don't see any toxicity, but bear in mind these mercury 4 levels are pretty high, so it's probably a prudent 5 thing to keep an eye on these people and make sure 6 they're not getting mercury toxin. 7 Q And they should do that, Doctor, because the 8 medical profession knows that there's a long latency 9 period between mercury exposure and injury, correct? 10 A Well, I don't think that was the crux of 11 what they were saying. I think what they were saying 12 is look, these levels are pretty high, and so when you 13 expose somebody to high levels of something even 14 though you don't see any sign of toxicity it is good, 15 particularly when you expose them, to keep an eye on 16 them. 17 I didn't see anything in here about raising 18 particular concern about latency because these people 19 were treated over a period of time, so that would have 20 included, you know, any latency for effect to occur. 21 Q But prolonged latency is known to medical 22 professionals, and you know it, correct? 23 A There is a latency period, yes. 24 Q And it's quite long from time of exposure to 25 the time when injury can occur, correct? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Well, it depends on the dose, it depends on 2 the circumstances of the exposure. Could be months. 3 Q Could be months. 4 A Yeah. 5 Q In fact, for the Iraqi grain contamination 6 cases it was months, wasn't it? 7 A Yeah, months. 8 Q Months at the very high dose, correct? 9 A Could be months, yes. 10 Q So, if we go to the next article that you 11 speak of, Axton, which is contained at L, Tab 7, now, 12 in Axton you spoke of one six week old infant, but 13 this report actually involved six cases of poisoning 14 after a parental organic mercurial compound, and they 15 called it merthiolate, correct? 16 A Right. 17 Q Doctor, would you just generally describe 18 these cases to the Court? 19 A Sure. As I recall without stopping too fast 20 to read the whole article -- 21 Q Sure. Take your time. 22 A -- and I may have to stop to look up certain 23 points, but I recall that there were six cases here 24 with deaths. Five of them died. If you look at the 25 survivor, it's actually the youngest one of the whole Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 group that survived, and that individual received 2 about 13,000 micrograms of mercury and maybe as much 3 as 220,000 micrograms of mercury. 4 Do you have any other questions about this 5 article? 6 Q Yes. Let's just go over this. The first 7 one, these cases all involve chloramphenicol, an 8 antibiotic, correct? 9 A Yes. 10 Q And the antibiotic had been preserved with 11 thimerosal? 12 A Right, and I believe they had used too much 13 thimerosal in the reconstitution of the antibiotic. 14 It wasn't the standard amount. Yes. 15 Q Correct. Yes. Rather than grams they put 16 in kilograms. 17 A They used a lot of thimerosal. 18 Q They used a lot. Yes. 19 A Yes. 20 Q Doctor, in Case No. 1 a seven year old child 21 was administered the chloramphenicol IM, correct? 22 A Seven year old child, da, da, da, IM 23 chloramphenicol. Yes. 24 Q Yes. That means by injection, yes? 25 A Correct. Intramuscular injection. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q Yes. Then four days after administration 2 his right buttock was noted to be swollen and very 3 tender. 4 A Right. 5 Q Ten days after admission the skin over his 6 right buttock appeared necrotic. 7 A Right. 8 Q What does necrotic mean? 9 A It means the cells were dying. 10 Q Right. A similar area appeared on the 11 anterior aspect of the left thigh, both areas were 12 intramuscular chloramphenicol had been given. Is that 13 true? 14 A Correct. 15 Q Yes. And he died on the 21st day after 16 admission? 17 A Right. 18 Q And when they did a biopsy, Doctor, what did 19 they find on biopsy? 20 A Are you talking about biopsy or autopsy? 21 Q I'm sorry, autopsy. 22 A Okay. You want me to go over all the 23 autopsy findings? 24 Q Well, just let's go to this one. 25 A Go back to all the autopsy findings in this Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 child? 2 Q Yes. 3 A Oh, okay. Fine. Well, it says here he had 4 an ulcer covered by a black eschar, which is basically 5 dead skin, over the right side there. 6 Q How large was the ulcer? 7 A Ten centimeters. 8 Q And in inches? 9 A Five. 10 Q Five inches. A five-inch ulcer from being 11 injected with thimerosal? 12 A Right. It says the edge was undermined and 13 indurated, and the underlying muscles were brown and 14 necrotic. There was no free pus, and the changes 15 extended almost to the pelvic bone. A five centimeter 16 abscess containing thin brown material was found in 17 the left thigh. Muscle necrosis in this area was also 18 extensive. Areas of consolidation were found in both 19 lungs. The spleen was moderately enlarged. 20 The kidney was enlarged and pale. When they 21 did a histological examination, in other words stained 22 sections under the microscope, there were thrombi or 23 blood clots in blood vessels, there was an area of the 24 lungs which had infarcted or died, there was tiny 25 what's called petechial hemorrhages in the brain. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Then it talks about necrosis at the injection site. 2 In the kidneys microscopically there was 3 degeneration and necrosis in the tubules and blooming 4 of the proximal tubular cells, flattening of the 5 tubular epithelium, pigment casts, some inflammatory 6 aggregates in the kidney with some blood cells in the 7 kidney, and then they give the amount of mercury in 8 all these various samples that they assayed, which was 9 very, very, very high. 10 Q So there was no doubt that the death was 11 related to mercury, was there? 12 A No. This was due to the incorrect 13 constitution of the medication with too much 14 thimerosal. 15 Q Right. And the second case also given by 16 injection also had black necrotic areas where the 17 injection was given. Isn't that true? That would be 18 the next page, Doctor, page report 2. 19 A Right. I'm just looking at it. 20 Q Yes. It's on page 418 at the very top. 21 A Had an induration and the next day these 22 areas became black and necrotic at the injection 23 sites. Yes. 24 Q Okay. It says extended over an area of 25 approximately 12 x 6 centimeters on each thigh. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 A Right. 2 Q How big is 12 x 6 centimeters? 3 A 6 x 3 inches. 4 Q Three inches on each thigh. 5 A At the injection sites, yes. 6 Q Okay. Doctor, this child died, didn't he? 7 A Yes. 8 Q And the concentration that he received was 9 quite high? 10 A Huge. 11 Q Then the case report of the child who 12 survived. She was a six week old child, correct? 13 A Wait a second. Let me see. The survivor, 14 yes. She was Case No. 3, and that was six weeks old. 15 Q Yes. And she had the same problem, didn't 16 she, with the injection site becoming necrotic? 17 A Yes. 18 Q But she got sent home, didn't she? 19 A Initially, yes. 20 Q And they eventually brought her back in when 21 they discovered the extraordinary dose of thimerosal 22 in the chloramphenicol, correct? 23 A They found out that she had received this 24 very high dose, yes, and that's right, they brought 25 her back and readmitted her. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q Now, she was the only one out of these six 2 patients to survive, correct? 3 A That's correct. 4 Q They indicate a reason for why they believe 5 she survived, didn't they? If you look on the next 6 column, page 419, the next to the last paragraph. 7 A Right, right. I'm looking at it, I'm just 8 reading it. It's a classical dose issue. They think 9 that although she received a number of injections of 10 chloramphenicol for the treatment of her pneumonia 11 they think they weren't all contaminated with the very 12 high doses of thimerosal, some of them had the 13 appropriate doses of thimerosal. 14 Q So she was the lucky one. She got the lower 15 doses. 16 A That's correct. 17 Q The others all got the higher doses? 18 A That's correct. 19 Q And they all died? 20 A That's just what I was saying this morning, 21 the dose makes the poison. 22 Q Yes. Now, Doctor, you also talked about 23 Fagan. Do you recall that? 24 A Yeah. 25 Q Now, Fagan is contained at Respondent's Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Exhibit L, Tab 17. 2 A Just seeing if I might have my own copy 3 here. 4 Q Doctor, before you go to that can I just ask 5 you one last question on that child who survived? 6 A Yeah. 7 Q Any long-term follow-ups? 8 A Hang on. I'll take a look. As I recall it 9 was ambiguous about to what degree that she was 10 followed-up. They say that the cavity that had 11 resulted from the necrosis in the area of injection 12 healed up in two months, and at that point her 13 physical signs were normal on examination and she 14 showed no signs of mercury toxicity. 15 Q That was at what? The end of two months? 16 A Two months. 17 Q Two months? 18 A Yes. 19 Q So if we could move on to Exhibit 17, which 20 is the Fagan article? 21 A Sure. 22 Q Okay. Now, Doctor, in Fagan there are 13 23 cases of, they call it omphaloceles. 24 A Omphaloceles. 25 Q Omphaloceles. And could you tell the Court Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 what omphaloceles are? 2 A Sure. You know, normally at postpartum 3 there is an umbilical stump and when the umbilical 4 cord is cut that stump becomes naturally necrotic. 5 Now, sometimes instead of that happening and it 6 involuting and go away it becomes large and 7 potentially problematic. 8 At the time what they were doing is they 9 were treating these omphaloceles by putting large 10 amounts of thimerosal tincture on the omphaloceles to 11 get them to see if they would necrose and go away. 12 Q In many instances it was put on until the 13 children were old enough so that a primary closure 14 could take place. Wasn't that true? 15 A It's possible. I don't recall. I could 16 look that up in the paper if you'd like. 17 Q Okay. If you'd like. 18 A I'll take your word for it. 19 Q Okay. Doctor, out of these 13 cases 10 of 20 them died, didn't they? 21 A Right. 22 Q They did an autopsy on these patients and 23 they had very high mercury levels, didn't they? 24 A Huge. They got highly overexposed to 25 mercury. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 Q But there was one child that they were able 2 to find who survived, correct? Out of the three 3 survivors they found one. 4 A Okay. 5 Q If you go to page 963 on the bottom it talks 6 about that one survivor, doesn't it? Last paragraph. 7 A Under discussions? 8 Q Yes. Last paragraph on the right-hand side. 9 A On the right-hand side. We traced one of 10 the survivors. They did a neurological exam 10 years 11 of age, and they looked for evidence of mercury 12 toxicity looking for visual field narrowing, which is 13 what you'd expect to see, or paresthesia, which you 14 would expect to see. They didn't assess intellectual 15 development, but they said the school reports that he 16 was restless, easily distracted and not interested in 17 schoolwork. 18 Q So the one survivor, Doctor, they couldn't 19 comment on his intellectual development, and his 20 school says he's restless, easily distracted and not 21 interested in schoolwork, correct? 22 A Right. Not very unusual for a 10 year old. 23 No objective signs of mercury toxicity, though. 24 Q And, Doctor, you mentioned one other case 25 where there was a poisoning and that was the Zhang Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 case. 2 A Uh-huh. 3 MS. CHIN-CAPLAN: The Zhang case is 4 contained at Exhibit 60. 5 SPECIAL MASTER HASTINGS: Tab 60? 6 MS. CHIN-CAPLAN: Tab 60. 7 SPECIAL MASTER HASTINGS: Okay. 8 BY MS. CHIN-CAPLAN: 9 Q This was a grain contamination case in 10 China, wasn't it? 11 A Yeah. Let me just bring up my copy here. 12 Q With ethyl mercury? Yes? 13 A I think I have my own copy. Yes, that's 14 right. This was a paper from 1984 from the Peoples 15 Republic in China in Zhang of grain contamination with 16 ethyl mercury. 17 Q Yes. Doctor, you stated in your opinion on 18 page 17 that 40 of the 41 patients who were exposed, 19 they improved or completely recovered despite the fact 20 that they received estimated doses between 35,000 and 21 280,000 micrograms of ethyl mercury. 22 A Uh-huh. 23 Q Now, Doctor, 40 out of 41 did not recover, 24 did they? 25 A I believe -- they went through the math -- Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 that was the case. If I could take a look at my 2 report there about this? What page are you on? 3 Q It's on page 256. 4 A Okay. What page of my report? 5 SPECIAL MASTER HASTINGS: Page 18 of your 6 report. 7 THE WITNESS: Okay. Yes. Thank you. Let's 8 see. 9 SPECIAL MASTER HASTINGS: Well, it's from 17 10 to 18. 11 THE WITNESS: Yes. I see. Thank you very 12 much, Special Master. They improved or recovered. 13 BY MS. CHIN-CAPLAN: 14 Q If you look on page 256, the first full 15 paragraph, it says in addition to the 27 cases treated 16 with chelation there were 13 cases that were not 17 treated. Two months later the untreated patients 18 showed little improvement in symptoms and signs. One 19 case deteriorated with the appearance of pathological 20 reflexes. These results indicate that chelation 21 therapy was valuable, albeit with a prolonged clinical 22 course. 23 So long as mercury persists in tissues 24 continued chelation therapy is recommended. So, 25 Doctor, when you said 40 out of 41 improved that's not Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 true, is it? 2 A Let me take a look here. I have to go 3 through the paper and see exactly what I was referring 4 to here. It said one patient died, the other 40 5 patients still showed a variety of clinical 6 manifestations after five months. 7 SPECIAL MASTER HASTINGS: Where are you 8 reading from that? 9 THE WITNESS: That is on the bottom of page 10 253. 11 SPECIAL MASTER HASTINGS: All right. 12 THE WITNESS: So they had clinical 13 manifestations at five months, but I think if you go 14 through the paper that you will find that they were 15 sicker when they came in. 16 BY MS. CHIN-CAPLAN: 17 Q Doctor, on page 256, didn't I just read to 18 you that there were 13 cases that were not treated 19 with chelation, two months later the untreated 20 patients showed little improvement in symptoms and 21 signs? 22 SPECIAL MASTER HASTINGS: That's at the top 23 of page 256? 24 MS. CHIN-CAPLAN: That's correct. 25 THE WITNESS: In addition to the 27 cases -- Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS 1 there were 13 cases that were not treated. Two months 2 later one case deteriorated. Right. That's at two 3 months. Let me just take a look here. But then if 4 you go to page 253 they talk about five months out, 5 and they say the other 40 patients still showed a 6 variety of clinical manifestations. 7 You look at these clinical manifestations, 8 and so, yes, they still have some clinical 9 manifestations. Some of them recovered, some of them 10 still have clinical manifestations. They clearly did 11 not appear to be as sick as when they came in. 12 MS. CHIN-CAPLAN: Okay. Special Master, I 13 think this is a good time to break. I'm going to 14 start another line of questioning. 15 SPECIAL MASTER HASTINGS: How long do you 16 anticipate being? I didn't know if we should go 17 through and finish with Dr. Brent. 18 MS. CHIN-CAPLAN: I may still have quite a 19 bit. 20 SPECIAL MASTER HASTINGS: All right. Let's 21 take our luncheon break at this point. 22 (Whereupon, at 1:10 p.m., the hearing in the 23 above-entitled matter was recessed, to reconvene this 24 same day, Friday, June 22, 2007, at 2:10 p.m.) 25 // Heritage Reporting Corporation (202) 628-4888


2438 1 A F T E R N O O N S E S S I O N 2 (2:12 p.m.) 3 SPECIAL MASTER HASTINGS: All right. We're 4 back from our luncheon break, and we're going to 5 proceed with the testimony of Dr. Brent. Cross- 6 examination by Ms. Chin-Caplan will proceed at this 7 point. 8 Please proceed, Ms. Chin-Caplan. 9 MS. CHIN-CAPLAN: Thank you, Special Master. 10 Whereupon, 11 JEFFREY BRENT 12 having been previously duly sworn, was 13 recalled as a witness herein and was examined and 14 testified further as follows: 15 CROSS-EXAMINATION (RESUMED) 16 BY MS. CHIN-CAPLAN: 17 Q Doctor, in your opinion does mercury have an 18 effect on the immune system at all? 19 A That's a very good question. The issue 20 there is exactly the same as the other issues that 21 we've discussed about this morning. It depends 22 totally on the dose, and the circumstance of the 23 exposure and the form of mercury. So, yes, at high 24 doses mercury can effect the immune system in many 25 different ways. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 In contrast, there's no suggestion 2 whatsoever that the doses of thimerosal that one 3 receives through a vaccination would have an adverse 4 effect on the immune system. 5 Q So you would admit that mercury does have an 6 effect on the immune system? 7 A Under the appropriate circumstances of dose, 8 yeah. 9 Q You mean there has to be a high dose to 10 effect the immune system? 11 A It has to be a high enough dose to effect 12 the immune system. 13 Q And do we know what that high enough dose 14 is? 15 A Well, I think there's no question that it is 16 considerably in excess of that which we get from 17 vaccines because there's no evidence whatsoever of any 18 activation of the immune system associated with 19 vaccines. 20 Q Okay. Have you read this article, which is 21 Petitioners' Exhibit 81, Effects of Mercury on the 22 Immune System? 23 A If I could take a look at the article I'll 24 tell you. Thank you very much. The Powell article? 25 Q The sections on up until I would say Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Section 3? 2 A Yes, I've seen this article. 3 Q Have you read it, Doctor? 4 A From page to page? 5 Q No, no. 6 A I've read it in the past, yes. 7 Q Okay. So, Doctor, this article, which is 8 entitled Effects of Mercury on the Immune System by 9 Michael Powell and Per Holzman, does it indicate that 10 low concentrations of mercuric mercury reduces cell 11 viability as a function of glutathione content? 12 A Can you show me where you're reading from, 13 please? 14 Q Sure. It's under two, Toxic Effects on 15 Lymphoid Components and Immune Responses. 16 A Uh-huh. 17 SPECIAL MASTER HASTINGS: What page? 18 MS. CHIN-CAPLAN: On page 422. 19 SPECIAL MASTER HASTINGS: Thank you. 20 MS. CHIN-CAPLAN: You're welcome. 21 BY MS. CHIN-CAPLAN: 22 Q It says that, correct? 23 A I was trying to find the section that you 24 just read. 25 Q Okay. Second sentence. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A Shenker and colleagues? 2 Q Yes. 3 A Used peripheral blood, mononucleo cells to 4 argue that low concentrations of mercuric, that was 5 mercuric chloride, reduce cell viability as a function 6 of glutathione content with cells having low 7 intracellular glutathiones, which is monocytes, being 8 the most sensitive. You read that correctly. 9 Q Thank you. Doctor, in the next sentence 10 doesn't it indicate that different members of the 11 lymphoid cell population have different sensitivities 12 to mercury? 13 A Sure. 14 Q So the monocytes are apparently the most 15 sensitive, aren't they? 16 A Let's see. Well, once again, you're talking 17 about micromolar concentrations here, so you have to 18 bear in mind the concentrations that you're using. I 19 can't imagine that following a vaccination how any of 20 these cells could ever achieve an exposure to 21 micromolar concentrations. Also, bear in mind that 22 this is mercuric chloride. It's a totally unrelated 23 form of mercury. 24 Q The reason we use these doses is so we can 25 see a response. Isn't that correct? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A That's right. You have to get to a high 2 enough dose so you can see a response because if you 3 go down to a low dose there is no effect. 4 Q Now, this is from Dr. Aposhian's slide, page 5 6, and it talks about the sources and forms and 6 mercury. We have mercury vapor, methyl mercury and 7 thimerosal, correct? 8 A Well, he has methyl mercury, mercury vapor 9 and thimerosal, right. Three of them. Right. 10 Q And thimerosal turns into ethyl mercury, 11 which turns into mercuric mercury, which is what we're 12 dealing with, correct? 13 A Well, yes and no. It's a small amount of 14 the thimerosal will turn into mercuric mercury, yes. 15 Q Right. But as it becomes inorganic it's 16 mercuric mercury? 17 A That small proportion that becomes inorganic 18 is mercuric mercury, yes. 19 Q Right. And mercury vapor becomes mercuric 20 mercury, correct? 21 A Some proportion of mercury vapor becomes 22 mercuric mercury. 23 Q Yes. And methyl mercury becomes mercuric 24 mercury? 25 A Much less so. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Q Yes. These are the organic forms. Ethyl 2 mercury and methyl mercury are organic, and when they 3 become inorganic they become mercuric mercury. 4 A They become mercuric mercury, right. 5 Q So we're looking at mercuric mercury, the 6 inorganic form, correct, in this article? 7 A Right. 8 Q Right. Doesn't it indicate that the 9 monocytes are the most sensitive to mercuric mercury? 10 A Sure, but at concentrations way, way in 11 excess of anything that you'd ever get from a vaccine. 12 Q Okay. Then it indicates that the B cells 13 are next most sensitive, correct? 14 A Yes. 15 Q Yes. And the least sensitive are the T 16 cells? 17 A That's right. 18 Q So there's some hierarchy of sensitivity to 19 exposure to mercuric mercury? 20 A To mercuric mercury, yeah. Relatively high 21 concentrations of mercuric mercury. 22 Q Right. Doctor, if you'll go on to the next 23 page. Actually, let's continue on in that sentence. 24 It says electron microscopic examination of mercury 25 killed cells reveals condensation and fragmentation of Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 nuclei and finally, loss of membrane integrity, 2 features that are consistent with an apoptotic-like 3 cell death. What does apoptotic life cell death mean? 4 A Well, cells can die in one out of two ways. 5 There is a necrotic cell death and there is an 6 apoptotic cell death. Necrosis is generally when 7 something goes wrong that caused a cell to die. 8 Apoptosis on the other hand is a natural process. 9 It's one that we need to live. 10 It is also sometimes referred to as 11 programmed cell death. All our cells are programmed 12 to die so that they make room for new, healthy cells. 13 A classical example is our skin cells. We're 14 replacing our skin all the time. Because the top 15 layers die by apoptosis we get nice, new fresh skin 16 cells. We don't have the same skin cells we were born 17 with. 18 It's why leaves fall off trees in winter. 19 It's apoptosis. You know, our liver cells. You're 20 constantly regenerating new, healthy cells from cells 21 that have been around for a while, and get abused, and 22 starting to function abnormally and then they undergo 23 apoptosis. So apoptosis is a natural response, it's 24 part of normal physiology, we'd be in big trouble 25 without it and it is a preprogrammed cell death. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Q Okay. Does mercury lead to a cell death 2 that resembles a natural cell death? Is that it? 3 A No. It depends on the concentration, it 4 depends on the dose. If, for example, mercury is 5 given in low doses you don't see an effect. If you 6 get up to these kinds of doses on the other hand, 7 these kinds of exposures, then what they're talking 8 about here is that it induces apoptosis in these 9 cells. 10 Q Okay. If you go to the very next paragraph 11 it says that the lack of a toxic effect may not 12 preclude significant functional impairment of a cell 13 population. So even though it doesn't kill it it 14 could effect the way it functions, correct? 15 A Well, they may, and I think this is 16 indicating that it may or may not depending upon what 17 the evidence is. It doesn't say it does. Once again, 18 you know, it's all a question of dose because what 19 they are talking about here, and once again, remember 20 we're talking about mercuric chloride not thimerosal 21 or ethyl mercury, and they're talking about doses that 22 these cells would never be exposed to in the body. 23 Q Doctor, if you move on to page 425 of this 24 article, the very first sentence, it says reductions 25 in both humoral and cell-mediated immune responses. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 That's both arms of the immune system, correct? 2 A That's correct. 3 Q In a number of species were reported 4 following exposure to organic and inorganic 5 mercurials. So whether it's organic or inorganic 6 doesn't seem to matter, it affects both arms of the 7 immune system? 8 A Well, that's true. You can get effects. 9 They won't necessarily be the same, but you can 10 definitely get effects with the various organic 11 mercurials or the inorganic mercurials at the 12 appropriate dose. 13 Q Okay. The mechanism by which mercury 14 elicits immunosuppression, particularly its responses 15 toward infectious agents, remains unclear and warrants 16 further study. More recent studies, particularly in 17 rodents, have suggested that the genetic background 18 may be a key player in understanding how mercury can 19 tilt immunoregulation towards immunosuppression or 20 immunostimulation. I've read that correctly? 21 A Yes. You did it very well. 22 Q Thank you. You wouldn't disagree with that, 23 would you? 24 A No. There's a lot of data on genetically 25 altered rodent models that show unusual responses to Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 mercury, so no. 2 Q So your genetics can determine whether 3 you're going to be resistent to mercury, or whether 4 you're going to be immunosuppressed, or perhaps even 5 whether you're going to tilt toward autoimmunity, 6 correct? 7 A If you're a rodent. 8 Q Right. If you're a rodent. 9 A Yeah. 10 Q Okay. Now, there have been other articles 11 written on mercury and its effect on the immune 12 system, haven't there? 13 A There's a huge literature on mercury in the 14 immune system. 15 Q Yes, there is, and you attached a few to 16 your opinion letter, didn't you? 17 A I think so. 18 Q Yes, you did. On Attachment 51 there's an 19 article by B.J. Shenker entitled Immunotoxic Effects 20 of Mercuric Compounds on Human Lymphocytes and 21 Monocytes. I. Suppression of T-Cell Activation. 22 SPECIAL MASTER HASTINGS: Which tab was 23 that? 24 MS. CHIN-CAPLAN: Fifty-one. 25 SPECIAL MASTER HASTINGS: Thank you. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 MS. CHIN-CAPLAN: You're welcome. 2 Are you there, Doctor? 3 THE WITNESS: Yes. I'm just looking to see 4 if I have it on my -- yes. 5 BY MS. CHIN-CAPLAN: 6 Q Now, this article looked at methyl mercury 7 and mercuric mercury, correct? 8 A Right. 9 Q And what it says in the middle of that 10 paragraph is that both forms of mercury caused a dose 11 dependent reduction in T-cell proliferation, however, 12 the effect was dependent upon the presence of 13 monocytes. In the absence of monocytes mercuric 14 mercury enhances PMA induced T-cell proliferation. 15 So it sounds like here, Doctor, and please 16 correct me if I'm wrong, if you don't have any 17 monocytes your immune system is in more trouble than 18 if it did have monocytes? 19 A Are you reading from the first page in the 20 abstract? 21 Q Yes. 22 A Both forms of mercury? Hang on. Let me 23 take a look. Here it is. Once again, remember this 24 doesn't deal with ethyl mercury or thimerosal, and of 25 course there's no dose discussion here, but, yeah, you Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 can get a diversity of effects. Certainly. 2 Q Okay. In this article it also indicates 3 that methyl mercury is five to 10 times more potent 4 than mercuric mercury, correct? 5 A You're still on the first page? 6 Q Still first page. 7 A In this particular scenario that they've 8 described in the prior sentence, yes. 9 Q Right. Five to 10 times more potent. 10 A Right. 11 Q So the organic methyl is five to 10 times 12 more potent than the inorganic mercuric mercury? 13 A Right. 14 Q Okay. Doctor, if you go on to the next page 15 it says at the very top there the results of this 16 investigation clearly show that mercury-containing 17 compounds are immunomodulatory; moreover, the decrease 18 in T-cell function following exposure to mercury 19 indicates that this metal is immunotoxic at very low 20 exposure levels. I read that correctly? 21 A You've read that correctly. 22 Q Do you agree with that? 23 A Well, once again, they didn't define what 24 they mean by very low exposure levels. I point out 25 again this has never been shown, that the exposure Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 levels you get from ethyl mercury in the vaccine, but 2 it depends on how they're defining low exposure 3 levels. I don't think they had the vaccines in mind 4 when they wrote this. 5 Q I agree with you. All right. So let us 6 continue, and actually, it's an article that dates 7 back to 1992, correct? 8 A It is. 9 Q At that time it was unknown that vaccines 10 contained mercury. Isn't that true? 11 A It was unknown that the vaccines contained 12 mercury? 13 Q Right. 14 A No. 15 Q In 1992? 16 A In 1992, of course it was known. 17 Q It was known? 18 A Yes. 19 Q Okay. So, Doctor, if you continue on in the 20 introduction, the third sentence. Epidemiological 21 surveys and laboratory studies have shown that when 22 individuals are exposed to low concentrations of heavy 23 metals the clinical symptoms appear to be "silent" or 24 asymptomatic. However, when the health status of 25 asymptomatic subjects is followed for long time Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 periods, there is clear evidence of tissue or organ 2 dysfunction. 3 A Well, I have no idea what heavy metal 4 they're talking about here. I can't think of a single 5 paper with mercury that would suggest this, and 6 certainly there's no reference here for what they're 7 talking about. 8 Q Well, Doctor, this article is on mercuric 9 compounds, isn't it? 10 A Yeah, and they talk about heavy metals. 11 They don't talk about mercury here. 12 Q Isn't mercury a heavy metal? 13 A Yes, but not all heavy metals are mercury. 14 Q True, but don't most heavy metals have an 15 effect on the immune system? 16 A At appropriate doses most heavy metals have 17 effects on the immune system, yes. 18 Q Okay. Then, Doctor, further down in the 19 third paragraph there's a very long list of what 20 studies of mercury immunotoxicity have indicated could 21 occur, right? 22 A Right. 23 Q It says Nakatsuru demonstrated that murine 24 lymphocytes when cultured with mercurials mitogen 25 induced DNA synthesis was inhibited, correct? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A Right. 2 Q And methyl mercury was 10 times more potent 3 than mercuric mercury? 4 A Uh-huh. 5 Q So the organic was 10 times more potent than 6 the inorganic, but the inorganic still had an effect? 7 A The methyl. 8 Q Yes. Then Nordlind demonstrated that both 9 murine thymocyte and splenocyte DNA synthesis were 10 inhibited by mercuric mercury. When they say 11 thymocyte and splenocyte are they referring to the 12 organs the thymus and the spleen? 13 A They are referring to the cells of the 14 thymus and the cells of the spleen. 15 Q And those are immune forming cells, aren't 16 they? 17 A More the spleen cells than the thymus cells. 18 Q They are? They're part of the immune 19 system? 20 A Yeah. 21 Q So the cells producing are affected 22 according to this individual? 23 A Well, you know, once again, I think we can 24 go through many, many, many papers on mercuric 25 chloride, and methyl mercury and the effects on the Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 immune system. There's a huge literature out there. 2 That literature all says yeah, there's a lot of 3 effects of methyl mercury, there's a lot of effects of 4 mercuric chloride on the immune system. 5 But that is not ethyl mercury, it's not even 6 thimerosal, and none of this really indicates doses of 7 exposure that you'd expect to see with a vaccine. So 8 we could spend a lot of time going through all these 9 articles, and I will endorse all these statements, but 10 they're completely irrelevant to what we're discussing 11 today. 12 Q Okay. So your opinion is that all the past 13 literature that's been done on organic mercury and 14 inorganic mercury have no relevance to the ethyl 15 mercury that is contained within the vaccines that 16 eventually turn into inorganic mercury? Is that what 17 you're saying? 18 A I'm saying that if you want to enlighten 19 this discussion in the true scientific fashion about 20 what happened with ethyl mercury at doses associated 21 with vaccines then we should discuss literature on 22 ethyl mercury at exposures we see with the vaccine. 23 Now, I don't think we're going to have that discussion 24 and the reason being there are no papers that show any 25 adverse effects. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 So we can go through the exercise of talking 2 about mercuric chloride, talking about ethyl mercury 3 and talking about high doses if you'd like, and I will 4 agree with all these statements to make it easier for 5 you. 6 Q Okay. Good. Then we can agree, also, that 7 T lymphocyte functions are affected in their responses 8 to mitogens and that mixed leucocyte responses were 9 depressed in mice and rats given mercuric chloride in 10 their drinking water or by subcutaneous injection, 11 correct? We can agree on that then? 12 A That's probably true. 13 Q Yes. And we can also agree then that when 14 they state all our results indicate that low doses of 15 mercury have a profound inhibitory effect on human T 16 lymphocyte activation. We can agree on that? 17 A Where are you reading from? 18 Q That's on page 541. 19 A You jumped ahead of me there. Right. So 20 the mercuric chloride and methyl mercury under 21 circumstances and doses not associated with vaccines, 22 but yeah, so I think that's probably true what they 23 say. 24 Q Okay. So low doses of any other mercury can 25 affect the immune system? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A No. We're talking micromolar doses here. I 2 don't think these are exposures that you're going to 3 get even if this was ethyl mercury. 4 Q Okay. But it says low doses, correct? 5 A Yes. 6 Q Of mercury? 7 A Correct, but not as low as vaccines. 8 Q So any other mercury other than ethyl 9 mercury can have a profound inhibitory effect on human 10 T lymphocyte activation? 11 A You can see effects with ethyl mercury, too, 12 but also at doses far in excess of what you get from a 13 vaccine. 14 Q Okay. Doctor, if we go on to the next 15 article, which is again an article by Shenker, and 16 we'll just do this very briefly. 17 A That's okay. 18 SPECIAL MASTER HASTINGS: When you say the 19 next article? 20 MS. CHIN-CAPLAN: Attachment 52. 21 SPECIAL MASTER HASTINGS: All right. Thank 22 you. 23 THE WITNESS: That's okay. Take your time. 24 BY MS. CHIN-CAPLAN: 25 Q Now, this study is a little bit of an Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 expansion from the last one, isn't it? 2 A I'll tell you in a second. They're both the 3 1992 Shenker article. Okay. 4 Q Okay. It's a little bit of an expansion? 5 A Well, it looks like the same experiment. 6 They're talking about two different aspects of the 7 same experiment, the first dealing with 8 immunosuppression and the second dealing with 9 alterations in cell viability. 10 Q Right. The last one didn't indicate how 11 long it took for these cells to be affected, did it? 12 A As I recall in the last one if you took the 13 methyl mercury and you applied it to mitogen, because 14 remember this is mitogen stimulated cells, so you put 15 the mitogen on, stimulate the cells. Put the mitogen 16 on and methyl mercury on at high doses, then you get 17 suppression of cell stimulation. 18 However, once you go out a couple of hours 19 that suppression is lost. In fact, if you look at 20 this first Shenker article once you go out about 24 21 hours that suppression is totally 100 percent gone. 22 So this is a very, very transient effect that has no 23 persistence in terms of time. 24 Q Well, this Shenker article doesn't say that, 25 though, does it? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A I think it does. In one of the Shenker 2 articles it does, and I believe it was this one. 3 Yeah. 4 Q This is the Immunotoxic Effects of Mercuric 5 Compounds on Human Lymphocytes and Monocytes. 6 Alterations in Cell Variety. 7 A No, and I said if you look at the first 8 article, the one on suppression, you can see that. 9 That's in Figure 3 of the article. 10 Q Okay. But in this article, Doctor, in the 11 abstract it says following treatment with mercuric 12 mercury or methyl mercury there was minimal reduction 13 in lymphocyte viability at one to four hours. 14 However, after exposure to mercury for 24 hours cell 15 death was apparent. In comparison, monocytes 16 exhibited significant loss of viability during the 17 early exposure period. 18 Again, it says methyl mercury is five to 10 19 times more potent than inorganic mercury, correct? 20 A I think at these concentrations it's 21 probably true. 22 Q So, Doctor, you would agree then that 23 mercury does have an effect on the immune system? 24 A I think I've been saying that all along, at 25 the appropriate dose, conditions -- Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Q Now, your contention is that this does not 2 involve ethyl mercury? 3 A Well, I have two concerns about a dialogue 4 about this data as it applies to the questions that 5 are relevant to these proceedings. One is that we're 6 not talking about ethyl mercury, and the second is 7 that we're not talking about exposures that are 8 related to exposures that you get from the vaccine in 9 terms of dose and concentration. 10 Q So, Doctor, if you had designed the 11 experiment what would you design it as? 12 A Well, I would do a number of things. The 13 first thing I would do is I would begin the way you 14 begin in science with cheap and dirty to see if 15 there's anything there, and so I would do an in vitro 16 experiment just to see if there's anything there to 17 test in the animal like the Agrawal study. 18 Now, in doing that the Agrawal study clearly 19 demonstrated -- except I would have done it with ethyl 20 mercury, but they used thimerosal -- that at exposures 21 you get from thimerosal the doses don't have an immune 22 effect, so at that point I would stop. I would say we 23 don't even see it in this in vitro study, we're 24 certainly not going to see it in the animal. 25 Although, the one thing I would have done Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 different is I wouldn't use ethyl mercury, I would 2 have used a more relevant exposure. So I think the 3 best data we've had is that it doesn't happen, but if 4 you want to do the perfect experiment that's the way I 5 would do it. 6 It's also perfectly possible to assess 7 immune parameters in thimerosal exposed people. That 8 can be done. It's very easy to do. We're still 9 exposing people to thimerosal. I had a patient about 10 two weeks ago who had a rattlesnake bite, and the 11 rattlesnake antivenom that we use has thimerosal in 12 it, and we gave it to the patient. 13 There's patients out there. A lot of people 14 all over the world are being vaccinated with 15 thimerosal containing vaccines. So it's very easy 16 even in humans to study various parameters of the 17 immune system and to assess whether you see an adverse 18 effect associated with thimerosal administration, but 19 there's not one documentation that there is. 20 Q Now, Doctor, you indicated that the Agrawal 21 study involved thimerosal? 22 A Thimerosal. 23 Q Yes. Were you present when Dr. Aposhian 24 indicated that thimerosal turns almost instantly into 25 ethyl mercury and these other components? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A Well, we know that happens in the body. In 2 fact, some of it happens in the bile as I testified to 3 before. Whether that happens under the conditions of 4 the Agrawal experiment is not clear, and they did not 5 assay that. 6 Q Okay. When you talk about doing a study of 7 thimerosal ethyl mercury in the individual how would 8 you account for the fact that some people might be 9 more susceptible than other people? 10 A Well, I think if you're saying if we wanted 11 to determine if there's a susceptible population, I 12 mean, nobody's ever suggested or given data that there 13 was a susceptible population, but if we wanted to go 14 and investigate this further we'd just take a bunch of 15 people being immunized maybe in parts of the world 16 where they're still using thimerosal and assess their 17 immunological parameters. 18 Q Now didn't the earlier Shenker article 19 indicate that people who are affected by mercury might 20 be more susceptible than others or cells rather? 21 A Different types of cell types have different 22 susceptibilities. 23 Q Uh-huh. But didn't it also indicate that 24 individuals might also be more susceptible as in 25 hypersusceptibility? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A As far as we know, there is no 2 hypersusceptible individual population. That is 3 strictly speculation. 4 Q So you wouldn't say that there's a genetic 5 makeup that might make people more susceptible than 6 others to the effects of mercury? 7 A I know of no genetic finding that supports 8 that with the single exception of some very 9 preliminary findings on the CPOX 4 gene which really 10 have to do with porphyrin synthesis, and it's still a 11 gene that's present in a very large proportion of the 12 population compared to a typical hypersusceptibility 13 seen that's present in 12 to 15 percent of the 14 population. 15 Q So roughly 15 percent of the population 16 might be more susceptible to the effects of mercury? 17 Is that what you just said? 18 A No. Roughly 12 to 15 percent of the 19 population will have a pattern of porphyrin synthesis 20 when exposed to mercury different from the other 85 21 percent. 22 Q What does that mean? 23 A As far as we know, nothing. 24 Q As far as we know, nothing? 25 A (Nonverbal response.) Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 SPECIAL MASTER HASTINGS: I'm sorry. You 2 need to say yes. 3 THE WITNESS: Yes, that's correct. As far 4 as we know, nothing. 5 BY MS. CHIN-CAPLAN: 6 Q Now, Doctor, you had talked about the Holmes 7 study in your presentation today. 8 SPECIAL MASTER HASTINGS: The which study? 9 MS. CHIN-CAPLAN: Holmes study. 10 SPECIAL MASTER HASTINGS: Holmes. 11 MS. CHIN-CAPLAN: Holmes, yes. I'll find 12 the citation for you. It would be Tab 27. 13 SPECIAL MASTER HASTINGS: Of his? 14 MS. CHIN-CAPLAN: Of his. 15 SPECIAL MASTER HASTINGS: Thank you. 16 MS. CHIN-CAPLAN: You're welcome. 17 BY MS. CHIN-CAPLAN: 18 Q Now, Doctor, we've already talked about this 19 or you've talked about it already in your presentation 20 today, correct? 21 A That is correct. 22 Q You indicated they hadn't been reproduced at 23 all. Is that true? 24 A That's right. That there was no public 25 study that supports it. Dr. Aposhian mentioned the Hu Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 study, but we had talked about the Hu study and it 2 clearly does not support the Holmes study. 3 Q Okay. Nobody's reproduced the study is what 4 you said, right? 5 A Well, people have tried. They haven't 6 gotten the same results. 7 Q You're probably referring to Ip, correct? 8 A And Kerns. 9 Q And Kerns. Okay. Now, in the Holmes study 10 she looked at first baby haircuts. Isn't that true? 11 A That's correct. 12 Q Before she looked at first baby haircuts 13 didn't she just look at the haircuts of the children 14 at the time that she saw them? 15 A I don't recall. Is that in the paper? 16 Q Yes, it is. 17 A Where is that? 18 Q On page 278. If you go down to the first 19 column, the next to the last paragraph, it begins with 20 in a clinical practice one of the study authors 21 submitted hair samples from autistic patients for 22 commercial laboratory testing for toxic metal 23 exposure. Most of these mercury hair levels were 24 found to be low contrary to a first order hypothesis 25 of heavy metal toxicity in autism. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 She then asked patients to submit first baby 2 haircut samples for analysis thereby testing a sample 3 that would more accurately reflect early exposure, 4 correct? 5 A Uh-huh. 6 Q Now, hair grows at approximately, what is 7 it, half inch a month? 8 A A centimeter a month, yeah. 9 Q So if you had a seven year old child the 10 hair that you need to be testing would be how long? 11 A No. Are you talking about the fact that it 12 would be to get the baby hair? 13 Q Yes. 14 A It's clearly not baby hair. 15 Q Yes. It's clearly not baby hair? 16 A Right. 17 Q So when she tested hair that was not baby 18 hair she got virtually nothing? 19 A Well, no. She says right here that when she 20 tested hair samples in general the results were very 21 low, and then she reports in which on her first baby 22 hair test the results are very low. So she's saying 23 here that general hair does the same thing as the baby 24 hair tested. 25 Q Okay. When you look at Ip, does Ip look at Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 first baby hair? 2 A No. 3 Q Ip looks at hair that's of seven year old 4 children, don't they? 5 A I can take a look at the paper. Let's see 6 if I have a copy on my computer. 7 Q It's the next one. It would be Tab 32. 8 A Okay. 7.2 years for the autistic spectrum 9 disorder group and 7.8 years for the control group. 10 Q Were they, what, seven years old? 11 A Approximately. 12 Q So at seven years old the hair that they 13 would need would have to be very long, wouldn't it? 14 A It's not baby hair. 15 Q Right. It's not baby hair. 16 Q So it would be hard to say that this really 17 contradicts the Holmes study, wouldn't it? 18 A I think it definitely contradicts the Holmes 19 study because even Holmes as you have pointed out 20 showed that when you don't look at baby hair she 21 thinks that the results are very low, and here we see, 22 no, you just track these cases seven years and the 23 results aren't very low. 24 Q Now, would you go to Kerns? I'm sorry. 25 Kerns is 34. Is Kerns a hair test? It's a hair Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 study? 2 A Yes. 3 Q It is a hair study? 4 A Yes. 5 Q Yes. But it looked at heavy metals in 6 general, didn't it? 7 A Heavy metals including mercury. 8 Q Right. If you look at the abstract doesn't 9 it indicate that the evidence from our study supports 10 the notion that children with autism may have trouble 11 excreting these metals resulting in a higher body 12 burden that might contribute to symptoms of autism? 13 A Hang on a second. 14 Q It does say that in the abstract, right? 15 A Hang on a second. I'm just bringing up my 16 copy of the paper here. Okay. I'm sorry. You were 17 looking at the abstract? 18 Q Yes. 19 A Right, but not mercury. He was talking 20 about arsenic, cadmium and lead were significantly 21 lower in the hair of children with autism than in 22 matched controls. With mercury there was no 23 difference. 24 Q So everything other than mercury? 25 A In this particular study. Now, another Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 study has contradicted even I believe the arsenic, 2 cadmium and lead data. 3 Q Okay. So, Doctor, there's one study that 4 you didn't mention that Dr. Aposhian did mention, and 5 that was the Adams tooth study. 6 A Yes. Okay. 7 Q In the Adams tooth study wasn't there the 8 indication that the teeth of autistic children had two 9 times more mercury than controls? 10 A Well, that's what they reported. Let me 11 pull out the study because I'd like to make a couple 12 of observations about that study. I'm very familiar 13 with that study, and there's a couple of things about 14 it I want to point out. 15 SPECIAL MASTER HASTINGS: Does anyone have 16 the citation from our record? Thank you. 17 Petitioners' Exhibit 82 I believe. 18 (Pause.) 19 BY MS. CHIN-CAPLAN: 20 Q Doctor, my question to you was wasn't it 21 shown in this article that autistic children had two 22 times the amount of mercury in their teeth as opposed 23 to normal children? 24 A Well, that's what they reported. 25 Q Okay. And would that be an indication that Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 autistic children have difficulty excreting mercury? 2 A No, for a number of reasons. Number one, 3 teeth, like hair, are not a normal excretory organ for 4 mercury. We don't lose a lot of mercury through our 5 hair. Teeth specifically, you know, a tooth is 6 basically bone. It's basically bone. We don't 7 incorporate mercury very much into bone, so I'm not 8 exactly sure what they're even looking at, but it's 9 just the opposite of what they see in hair. 10 I mean, the Holmes people have reported, 11 although it couldn't be replicated, that there's low 12 release of mercury through the hair. Even if that 13 were true how do you reconcile it with this study 14 which shows there's an increased release of mercury 15 through the teeth? It doesn't make any sense. Now, 16 the truth is with this study I'm not sure their 17 results are statistically significantly different 18 based on the statistical tests they did because they 19 do have an error in their statistical methodology. 20 I don't know if you want me to go into it. 21 I'll be glad to if you'd like. 22 Q Doctor, you're saying that teeth are an 23 excretory organ? 24 A No. 25 Q It's tissue, isn't it? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A Teeth, like hair, are not excretory organs 2 for mercury. It is known that some organic mercury 3 gets incorporated in hair. Teeth is more analogous to 4 bone, and you don't usually get mercury in bone. 5 Q It's tissue, correct? 6 A Well, it's a tooth. 7 Q Yes. It's tissue, and it's tissue that 8 contains two times more mercury in autistic children 9 than in that of normal children? 10 A Well, I'm not sure it's even a statistically 11 significant difference. The group size is small. I 12 can go into that if you'd like, and it doesn't have 13 any meaning. If anybody wanted to know do autistic 14 children have more mercury than nonautistic children 15 all they have to do is get blood levels or get urine 16 levels on the autistic children. 17 I mean, I know so many autistic children 18 have had this done. Nevertheless, there's not one 19 single study in the peer-reviewed English language 20 literature that reports a difference in blood mercury 21 level in autistic children or in urine levels in 22 autistic children compared to controls, and so I don't 23 know what to make of it. Teeth. It doesn't make any 24 sense. I'm not even sure it's a statistically 25 significant difference. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Q Now, Doctor, you're familiar with the 2 Burbacher study, aren't you? 3 A Burbacher study? Yes. 4 Q Burbacher study. Yes. That was a study 5 done on primate monkeys? 6 A Yes. 7 Q That was a situation where they tried to 8 recreate the vaccine schedule. Was that it? 9 A Yes. 10 MS. CHIN-CAPLAN: Let me find it for you. 11 Twelve. 12 SPECIAL MASTER HASTINGS: I'm sorry? 13 MS. CHIN-CAPLAN: Twelve. 14 SPECIAL MASTER HASTINGS: Tab 12. 15 MS. CHIN-CAPLAN: Yes. 16 SPECIAL MASTER HASTINGS: Of Dr. Brent? 17 MS. CHIN-CAPLAN: Dr. Brent. 18 SPECIAL MASTER HASTINGS: All right. Thank 19 you. 20 BY MS. CHIN-CAPLAN: 21 Q So, Doctor, tell the Court what this study 22 consists of. 23 A Sure. I would be glad to. Thank you. This 24 was a comparison of mercury levels in infant monkeys 25 who were given either dietary methyl mercury or Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 intramuscular thimerosal as in a vaccine. They did 2 the intramuscular injections once a week and gave over 3 a period of about three weeks roughly the amount of 4 thimerosal that an infant would receive in about six 5 months of vaccinations on a per kilogram basis. 6 Then they assessed the kinetics of what 7 happened following the exposure. In other words, 8 where the mercury went, what the rate of excretion 9 was, what was left behind, half-life, that kind of 10 thing. 11 Q They found out what the half-life was in the 12 primates at least for ethyl mercury, didn't they? 13 A Right. 14 Q And it was comparable to what has been noted 15 in humans, correct? 16 A Very, very close. It was about eight days. 17 Q Yes. Did they measure the amount of mercury 18 that was in the brain? 19 A Yes, they did. 20 Q When they measured the amount of mercury 21 that was in the brain what was the comparison between 22 the inorganic mercury from methyl mercury exposure and 23 that of ethyl mercury exposure? 24 A Well, it depends on the timeframe. Ethyl 25 mercury entered the brain and then effluxed from the Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 brain. 2 Q It what? 3 A Effluxed. Left the brain. The other 4 process that goes on for both methyl mercury and ethyl 5 mercury is that there is some deorganification of the 6 mercury. In other words, it becomes inorganic 7 mercury. It happens a little bit more with ethyl 8 mercury than with methyl mercury. So as time goes on 9 there is faster loss in the brain with ethyl mercury 10 than with methyl mercury, but there's also faster 11 conversion of ethyl mercury to inorganic mercury in 12 the brain. 13 Q And the conversion of organic to inorganic 14 in the brain occurred with roughly three times the 15 amount for ethyl as opposed to methyl, wasn't it? 16 A I can give you the exact amount. Let me 17 just take a look here. It was more like twice the 18 amount, but you might be right. I'm just trying to 19 see where I can find it here in the paper. Well, I 20 can't find it right now. Instead of taking time 21 looking for it I thought it was twice as much, three 22 times as much, that ballpark. 23 Q Around three times more? 24 A Two or three times. Yes. 25 Q Right. So, Doctor, once it turns into Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 mercuric mercury or inorganic mercury in the brain can 2 it leave? 3 A There is an efflux. It's very, very, very 4 slow. 5 Q Dr. Aposhian had given this example about a 6 family who ate a pig that drank mercury, and when the 7 woman died 29 years later the mercury was still 100 8 times the normal amount that was seen. 9 A Yeah. This is a very highly exposed 10 population. They had a huge exposure to mercury, and 11 a number of the family members died and there's one 12 survivor who when she ultimately died still had a 13 significant amount of mercury in her brain. That's 14 correct. 15 Q So inorganic mercury can be pretty toxic to 16 the brain, correct? 17 A Well, not necessarily. You wouldn't 18 necessarily expect that because the bad news, Ms. 19 Chin-Caplan, is that you, and I and everybody else in 20 this courtroom have nontoxicologically consequential 21 but significant amounts of inorganic mercury in our 22 brain. As a matter of fact, every time we eat a 23 seafood meal we're getting a bolus, some of which 24 becomes inorganic mercury in the brain. 25 We know that if people ate through both Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 their diet, maybe to some degree from their dental 2 amalgams if they have it and from just the air around 3 us, which has mercury in it, we naturally accumulate 4 mercury in the brain, which becomes inorganic mercury 5 and stays there for a very long time, and that has no 6 pathological significance at all. 7 It doesn't cause an adverse effect unless 8 you get to very high levels, and there have been 9 multiple studies demonstrating that. So, yes, you get 10 inorganic mercury in your brain. You get inorganic 11 mercury in the brain from many, many, many different 12 sources. Not only people, every animal on the Earth 13 has a significant amount of inorganic mercury in the 14 brain because mercury is a naturally occurring 15 substance. It's in the air. 16 We've all developed very sophisticated 17 mechanisms to inactivate the mercury in the brain, and 18 you only actually can get an adverse effect from the 19 inorganic mercury in the brain if you have so much in 20 your brain that you overwhelm the very well-developed 21 defense mechanisms that we have. 22 Q Now, Doctor, you're a pediatrician, correct? 23 A I'm a toxicologist. 24 Q Did I also hear you say that you were a 25 pediatrician? Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A I'm a professor of pediatrics, but I'm a 2 medical toxicologist. 3 Q Okay. You do know that the nervous system 4 and the immune system of infants are continuing to 5 develop for the first two years of their lives, 6 correct? 7 A To some degree. 8 Q Yes. And during those first two years is 9 the same time that the thimerosal containing vaccines 10 are being administered, correct? 11 A They were. 12 Q Yes. So these vaccines are being 13 administered at one of the most vulnerable periods in 14 their lives? 15 A Yes, that's right, but very unlikely with 16 any ill effect. 17 Q How do you know that? 18 A Well, number one, there has never been, 19 other than the very, very rare allergy -- we're not 20 talking about allergy, you can get allergy with any 21 medication, I assume you don't want to talk about that 22 -- a demonstration that thimerosal in doses in 23 vaccines given to infants causes an adverse effect. 24 As you know this has been extremely well- 25 studied, this has been extremely well-scrutinized and Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 as a matter of fact it wouldn't even be plausible, and 2 I'll tell you why. It's a very interesting analysis 3 that was just published from Brazil where their 4 immunization schedule using thimerosal was pretty much 5 similar to the United States. 6 Q Did you say McGill? 7 A Brazil. 8 Q Brazil? 9 A Yes. The country Brazil. They looked at 10 the mercury exposure from breast feeding, and they 11 breast feed about the same amount in Brazil as they do 12 here, and from the thimerosal in the vaccines. It 13 turns out there's twice as much mercury exposure from 14 breast feeding as there is from ethyl mercury in the 15 vaccines. 16 So it's hard to imagine how the amount of 17 mercury that we get from breast feeding is going to 18 have an adverse effect or that the amount of mercury 19 that we get from vaccines is going to have an adverse 20 effect. 21 Q Well, Doctor, you are aware that there's at 22 least one breast feeding study that was done from the 23 Iraqi grain contamination cases, aren't you? 24 A Well, yeah, but those were very, very highly 25 exposed individuals. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 Q You must know that those babies did not 2 demonstrate ill effects for quite some time after they 3 were exposed? 4 A That's true, but this was following a very 5 large exposure. We've had a number of epidemiological 6 studies now, which I think will be discussed on 7 Monday, where children have been followed for long 8 periods of time following their thimerosal containing 9 vaccines and at least with regard to the question of 10 autism or ASD there's clearly no relationship based 11 on -- 12 Q Well, when you say there's no relationship 13 you're relying solely on the epidemiological studies? 14 Is that it? 15 A I'm relying on the epidemiological studies 16 and the fact that there's nothing to the contrary that 17 suggests there is a relationship. 18 Q However, the molecular study seems to 19 indicate that there is an effect, doesn't it? 20 A What molecular study? 21 Q Well, the studies that we looked at on the 22 immune system. 23 A At high doses of mercury chloride or methyl 24 mercury? 25 Q Yes, those studies. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A Well, no. You can't translate that to say 2 that low doses of ethyl mercury are going to have an 3 effect. 4 Q So you disagree with the statement earlier 5 that people could be asymptomatic from low doses, but 6 that further on in their lives that it would result in 7 symptomatic disease? 8 A Which statement was that? Was that the 9 reference statement about heavy metals? Is that what 10 you're referring to? 11 (Pause.) 12 Q Maybe it's Shenker. Yes, it's in Shenker. 13 A Was that the reference statement about heavy 14 metals? 15 Q Yes. It was on Tab 51 on page 540, and 16 you've already indicated with me that you agree with 17 these statements. 18 A Let me just take a look here. 19 Q It says epidemiological surveys and 20 laboratory studies have shown that when individuals 21 are exposed to low concentrations of heavy metals the 22 clinical symptoms appear to be silent or asymptomatic. 23 However, when the health status of asymptomatic 24 subjects is followed for long time periods there is 25 clear evidence of tissue or organ dysfunction. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 A That's a heavy metals statement, it's not a 2 mercury statement and it's completely unreferenced. I 3 have no idea what they're talking about. 4 Q Of course, the title of this article is 5 Immunotoxic Effects of Mercuric Compounds, correct? 6 A That's true. If they were talking about 7 mercury here in a specific study they would have said 8 mercury, and they would have cited the study. 9 Q So the fact that the title was on mercuric 10 compounds and they mentioned heavy metals makes you 11 think it's not mercuric compounds that they're talking 12 about? 13 A I think what they were trying to do is try 14 to generalize some other heavy metal and relate it to 15 mercuric compound. 16 Q Is there any reason to believe that mercury 17 does not act in the same manner as these other heavy 18 metals? 19 A Absolutely there are. There are no two 20 heavy metals that I can think of that have a similar 21 effect on the immune system. All of them at 22 appropriate doses will potentially have adverse 23 effects on the immune system, but they're different, 24 just like even different forms of mercury have 25 different effects on the immune system. Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 MS. CHIN-CAPLAN: Okay. Thank you, Doctor. 2 THE WITNESS: Thank you. 3 SPECIAL MASTER VOWELL: Dr. Brent, I have a 4 number of questions for you. This is Special Master 5 Vowell speaking. 6 THE WITNESS: Please. 7 SPECIAL MASTER VOWELL: You've used two 8 terms, as did I believe Dr. Aposhian, efflux and 9 hypersusceptibility. Would you define those terms for 10 me, and are you both using them in the same way? 11 THE WITNESS: Thank you very much for asking 12 that question. That's a great question. Efflux. I'm 13 not sure how Dr. Aposhian viewed efflux, but from the 14 context in which he was talking it was clear by the 15 fact that he was stating that he was discussing the 16 hair studies of Amy Holmes and the chelation study of 17 Bradstreet, and in fact he pretty much came out and 18 said this, and it's certainly what he said before the 19 IOM, that autistic children do not excrete mercury 20 well. 21 When we talk about in biological processes 22 molecules moving from one place to another they either 23 move in or they move out between compartments, and 24 efflux is basically moving out meaning out of the body 25 in this case. So his efflux disorder hypothesis is Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 that the hair studies of Holmes and the chelation 2 study of Bradstreet are pointing to the fact that 3 these kids don't excrete mercury, don't efflux it out 4 of their bodies. 5 SPECIAL MASTER VOWELL: So they retain it, 6 and therefore more would be available to work its ill 7 effects on whatever system we're talking about? 8 THE WITNESS: That's exactly the hypothesis. 9 Precisely. Now, hypersusceptible, Dr. Aposhian did 10 not really define what he meant by hypersusceptible 11 other than, and this is what I infer from his 12 testimony, some hypothesized group of children that 13 react to mercury to get toxic at doses that nobody 14 else in the world would ever get toxic to, so they're 15 hypersusceptible. 16 Because of that ambiguity in that testimony 17 is one of the reasons I drew up that bell-shaped curve 18 with the second curve showing the hypersusceptible 19 population. 20 SPECIAL MASTER VOWELL: Yes. 21 THE WITNESS: There is a formal 22 toxicological concept of hypersusceptibility, and 23 that's what I tried to illustrate by those curves and 24 to say that when there is a hypersusceptible 25 population we have a way of looking for it, we know Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 exactly what it is, although they've never been found 2 in the autistic group with regard to mercury. 3 SPECIAL MASTER VOWELL: That was the example 4 I think you used of Wilson? 5 THE WITNESS: Yes. That's exactly right. 6 That where there is hypersusceptibility to toxins very 7 often with not too much research we've actually 8 identified the hypersusceptibility. Wilson's disease, 9 hypersusceptibility to copper. We know the gene. 10 It's very clear. You can do a genetic test. They 11 either have it or they don't. 12 SPECIAL MASTER VOWELL: Bear with me for a 13 minute here. 14 THE WITNESS: Take your time. 15 SPECIAL MASTER VOWELL: In Dr. Aposhian's 16 testimony he talked about one in 500 children exposed 17 to the teething powder that caused acrodynia or Pink 18 disease developing the disease. Do you know how that 19 figure was derived, the one in 500? 20 THE WITNESS: Yes. Yes, I do. That I 21 believe derives back from one of the Dr. Warkany 22 articles. 23 SPECIAL MASTER VOWELL: Doctor? I'm sorry? 24 THE WITNESS: Warkany, W-A-R-K-A-N-Y. 25 SPECIAL MASTER VOWELL: Okay. The third Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 exhibit? 2 THE WITNESS: Yes. Well, he wrote a couple 3 of articles. I'm not sure if it's that exact one, but 4 it's from that body of research. That number has been 5 carried forward and requoted in the literature. 6 Basically, what that number is is that if you look at 7 kids who were exposed to mercurous chloride from the 8 teething powder not all of them get mercury toxic in 9 the form of acrodynia, only some of them do. 10 There are two potential explanations for 11 that. One is that it's a hypersusceptible population 12 that does, and the other, which would be the more 13 common reason in toxicology, is it's simply a matter 14 of dose. Some got more, some got less, and it's only 15 the ones that got quite a lot that came down with the 16 disease, so they got the high dose. 17 In fact, looking at that Warkany study that 18 the Court now has come up with that clearly 19 demonstrates that the children who get acrodynia have 20 very, very high mercury levels, so it appears to be 21 just simply a dose-related phenomenon. The reason 22 that not everybody got it is you had to get a 23 significant dose. 24 SPECIAL MASTER VOWELL: So you're not aware 25 of any study that looks at a dose response level to Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 teething powders? 2 THE WITNESS: No. There's never been a dose 3 response level. We only have the study that shows 4 that children that have it have a very high titer in 5 terms of urine mercury, but it's never actually been 6 looked at in terms of a formal dose response analogy. 7 SPECIAL MASTER VOWELL: Right. And this was 8 not a study then that said of 2,000 children in this 9 town, assuming all of them were teething and got 10 teething powders, one in 500 developed this disease? 11 THE WITNESS: No. 12 SPECIAL MASTER VOWELL: Okay. All right. 13 Let me move on to a couple of other questions then. 14 One is the term used in much of the medical literature 15 you and Dr. Aposhian cited to refer to toxic I guess 16 levels of mercury is mercury intoxication. Does that 17 term have -- at some point you can say someone is 18 mercury intoxicated? Can you explain that term for 19 me? 20 THE WITNESS: Absolutely. Intoxication 21 simply means having enough of the substance on board 22 that it is causing some kind of an adverse of a toxic 23 effect. Classic example is alcohol. We use the word 24 intoxication all the time. You just have enough on 25 board, you get alcohol intoxicated, then you start to Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 stagger and so on. 2 So toxicologically when you use the word 3 intoxication it simply means you've had a sufficient 4 exposure, you've had a sufficient dose, such that you 5 are now getting adverse effects from that substance. 6 SPECIAL MASTER VOWELL: Well, let me follow- 7 up on that compared to my previous question then. 8 THE WITNESS: Sure. 9 SPECIAL MASTER VOWELL: One of us could have 10 four drinks and the other have two drinks, each drink 11 containing the same amount of alcohol, and we would 12 have different reactions. One of us with four drinks 13 might be able to walk a straight line. If I had two 14 I'm sure I couldn't. Can you analogize the effects of 15 alcohol intoxication to mercury intoxication? 16 That if someone who is, for example, more 17 used to drinking, can walk that straight line at a 18 higher level of alcohol? 19 THE WITNESS: Yes. This is the bell-shaped 20 curve that we were talking about that if you look at 21 the dose of a substance, in this case alcohol, 22 necessary to cause a specific response, say walk a 23 straight line, that it's not going to be exactly the 24 same for everybody in the population, and that if you 25 look at enough people in the population it forms sort Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 of this bell-shaped curve where most people are going 2 to sort of be in the middle, two to three drinks 3 probably do it for most people, but for some people it 4 could be seven and for some people it could be one. 5 So that's how this curve -- 6 SPECIAL MASTER VOWELL: Okay. I'm not 7 articulating this well because I understand that. 8 What I'm getting at is if I'm used to drinking a great 9 deal and then I have two drinks the alcohol might have 10 a less apparent effect on me. 11 THE WITNESS: That's true. 12 SPECIAL MASTER VOWELL: So if someone is 13 exposed to low levels of mercury over a period of time 14 would they show intoxication, that is ataxia at the 15 same blood or urine mercury levels as someone else who 16 is getting a bolus dose? 17 THE WITNESS: I'm sorry. I misunderstood 18 your question. With alcohol there is a very well- 19 known phenomena, which I think everybody has had a 20 chance to see in people who drink a lot, it's known as 21 tolerance, where some people one or two drinks and as 22 we were saying you have an excess, but if people drink 23 quite a bit that curve shifts for them and they 24 develop a tolerance. 25 They could have six or seven drinks and, you Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 know, we'd never know they were drinking. That's 2 tolerance. It happens with alcohol, well, for several 3 reasons, metabolic adaptations and so on. There is no 4 similar tolerance with mercury. There are some minor 5 adaptations, but for the most part there is no similar 6 tolerance for mercury. 7 We already have our body's protection in 8 place and they can up regulate and down regulate a 9 little bit, but they don't change in a marked fashion. 10 SPECIAL MASTER HASTINGS: So while people 11 might fall at a different place in the bell curve the 12 fact that you were working at a thermometer 13 manufacturing plant would not have any effect on where 14 you would fall on that bell curve? 15 THE WITNESS: That's exactly right. 16 SPECIAL MASTER VOWELL: Okay. You've 17 indicated the different species of mercury have 18 different effects. At the level of intoxication how 19 are the effects of methyl mercury distinguished from 20 ethyl mercury in terms of clinical signs and symptoms? 21 THE WITNESS: Yeah. That's a very good 22 question. This might be in the record. There was a 23 major review on this subject by Tom Clarkson where he 24 had listed all the different kinds of mercury and the 25 clinical effects of the different kinds of mercury to Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 show how different they are. My reading of that 2 review is that it is a very good reflection of what I 3 believe to be in the literature. 4 So, for example, with methyl mercury almost 5 all of the effects are in the central nervous system, 6 in the brain, as with methyl mercury. With ethyl 7 mercury because of the rapid separation of the mercury 8 off the ethyl group then it generates this inorganic 9 mercury as we were talking about before. Inorganic 10 mercury tends to effect primarily the kidney. 11 That doesn't happen much with methyl 12 mercury. So with methyl mercury we would see at high 13 doses effecting the brain, low doses don't worry about 14 having your seafood dinner tonight, it's good for you. 15 Ethyl mercury on the other hand, similarly at high 16 doses you could see the effects in the brain if you 17 have a sufficient dose, but you will also see effects 18 of the kidney. 19 SPECIAL MASTER VOWELL: All right. Let's 20 leave aside the things that we're not going to observe 21 with our eyes. Let's just talk about the clinical 22 picture of the Iraqi farmer who ate the methyl mercury 23 contaminated wheat walks into a medical clinic along 24 with the Chinese farmer who ate the ethyl mercury 25 contaminated rice. How are their symptoms going to Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 differ at the level of intoxication? 2 THE WITNESS: Their central nervous system 3 symptoms would probably be the same, the tunnel vision 4 would probably be the same, the tremor would probably 5 be the same, the paresthesias would probably be the 6 same, but you would also see some renal effects, 7 abnormal renal function, in the ethyl mercury exposed 8 version. 9 SPECIAL MASTER VOWELL: Okay. Are the 10 amounts of ethyl mercury that would produce those 11 physically apparent toxic effects the same amounts as 12 ethyl mercury? 13 THE WITNESS: As methyl mercury? 14 SPECIAL MASTER VOWELL: Yes, as methyl 15 mercury. 16 THE WITNESS: Right. 17 SPECIAL MASTER VOWELL: I mean, if we're 18 comparing grain, rice, wheat, whichever we're eating, 19 does the amount of the ethyl mercury in the rice 20 differ from the amount of methyl mercury in the 21 wheat -- 22 THE WITNESS: Yeah. That was well-covered 23 in the Burbacher paper that we were just discussing 24 because one of the things that they considered was 25 this whole business about the difference between the Heritage Reporting Corporation (202) 628-4888


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BRENT - CROSS (RESUMED) 1 reference dose for methyl mercury in application to 2 ethyl mercury, and he pointed out that if you use the 3 reference dose for methyl mercury and apply it to 4 ethyl mercury you will over estimate its toxicity 5 compared to what it really is because you would expect 6 the ethyl mercury to be less toxic. 7 SPECIAL MASTER VOWELL: Okay. So if I 8 understand what you're saying it would take more ethyl 9 mercury to produce the same effect that you would see 10 with a smaller amount of methyl mercury? 11 THE WITNESS: Right. And in fact, that's 12 only experimentally shown. Laslo Magos published a 13 paper in 1985 where he gave animals equivalent doses 14 of methyl mercury and ethyl mercury and then higher 15 doses, and he showed that you need more ethyl mercury 16 to get a degree of damage to the brain than you need 17 methyl mercury. 18 SPECIAL MASTER VOWELL: If I ingest a 19 certain amount of ethyl mercury versus having it 20 injected, how does that impact the toxicity of the 21 substance? 22 THE WITNESS: Well, the toxicity will depend 23 on the blood level, and so you would probably get a 24 little higher blood level from an ingestion than you 25 would from an injection. Heritage Reporting Corporation (202) 628-4888


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BRENT - REDIRECT 1 SPECIAL MASTER VOWELL: I'm talking about 2 intramuscular injection. 3 THE WITNESS: That's exactly right. The 4 reason is because it's an intramuscular injection and 5 it's slowly absorbed you don't get very high blood 6 levels. 7 SPECIAL MASTER VOWELL: So intravenous 8 injection versus ingestion you would get a higher 9 level depending on how you were administering it? 10 THE WITNESS: Absolutely. 11 SPECIAL MASTER VOWELL: All right. I think 12 those are all my questions. Thank you very much, Dr. 13 Brent. 14 THE WITNESS: Thank you. 15 SPECIAL MASTER HASTINGS: Any redirect for 16 this witness? 17 MS. RENZI: I just have one question. 18 SPECIAL MASTER HASTINGS: Please go ahead. 19 REDIRECT EXAMINATION 20 BY MS. RENZI: 21 Q Dr. Brent, Ms. Chin-Caplan spent a great 22 deal of time this afternoon going through the 23 literature on mercury and its effect on the immune 24 system. At one point you said that you would agree 25 with any of the statements that she read from that Heritage Reporting Corporation (202) 628-4888


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BRENT - REDIRECT 1 literature to the effect of mercury on the immune 2 system. I know you've said this, but I want to make 3 it abundantly clear. 4 What significant caveats do you place on the 5 statement with respect to the form of mercury, and 6 also, the dose? 7 A Well, those are the two most important 8 considerations. I hope I haven't been redundant 9 today, but I really wanted to make these points. 10 They're fundamental points. 11 When we're talking about mercuric chloride, 12 when we're talking about methyl mercury, we're not 13 talking about ethyl mercury, we're not talking about 14 the exposures in vaccines, so you cannot assume that 15 all the statements, which I agreed with -- yeah, 16 methyl mercury at this concentration will cause that, 17 and mercuric chloride at that concentration will cause 18 something else -- have anything do with the exposures 19 to ethyl mercury. 20 The other issue of course is that ethyl 21 mercury we can make to have adverse effects on the 22 immune system. They won't be exactly the same as 23 methyl mercury or mercuric chloride, but it can be 24 shown to have some adverse effects on the immune 25 system, but you have to go once again to very, very Heritage Reporting Corporation (202) 628-4888


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BRENT - REDIRECT 1 high doses compared to anything that anybody could 2 possibly expect to experience from a vaccine. 3 So both of those concepts have to be taken 4 into consideration. You want to know about ethyl 5 mercury you have to ask what the data is on ethyl 6 mercury. If you want to know what happens in a 7 vaccine you have to ask what happens if the dose is 8 associated with a vaccine? 9 MS. RENZI: Thank you. I have no further 10 questions. 11 THE WITNESS: Thank you. 12 SPECIAL MASTER HASTINGS: Anything further 13 for this witness? 14 MS. CHIN-CAPLAN: No, Special Master. 15 SPECIAL MASTER HASTINGS: All right. Dr. 16 Brent, we kept you up there all day. We thank you 17 very much. You're excused at this point. 18 THE WITNESS: Well, thank you, Special 19 Master. 20 (Witness excused.) 21 SPECIAL MASTER HASTINGS: Before we break 22 for the day I understand that's all the testimony we 23 have for today. 24 Mr. Matanoski? 25 MR. MATANOSKI: That's correct, sir. Heritage Reporting Corporation (202) 628-4888


2494 1 SPECIAL MASTER HASTINGS: The schedule for 2 Monday is Dr. Griffin and Dr. Fombonne? 3 MR. MATANOSKI: That's correct. 4 SPECIAL MASTER HASTINGS: In what order? 5 MR. MATANOSKI: I believe it will be Dr. 6 Fombonne first, sir. 7 SPECIAL MASTER HASTINGS: Okay. All right. 8 So that's the witnesses we have for Monday, and that 9 will conclude the government's case I assume? 10 MR. MATANOSKI: That's the government's case 11 in chief, yes, sir. 12 SPECIAL MASTER HASTINGS: Case in chief. 13 Correct. Then we'll be adjourned for today. We'll 14 see you folks Monday morning at 9:00 a.m. Thank you, 15 all. 16 (Whereupon, at 3:32 p.m., the hearing in the 17 above-entitled matter was adjourned, to reconvene on 18 Monday, June 25, 2007, at 9:00 a.m.) 19 // 20 // 21 // 22 // 23 // 24 // 25 // Heritage Reporting Corporation (202) 628-4888


2495 REPORTER'S CERTIFICATE DOCKET NO.: 98-916V CASE TITLE: Theresa Cedillo v. HHS HEARING DATE: June 22, 2007 LOCATION: Washington, D.C. I hereby certify that the proceedings and evidence are contained fully and accurately on the tapes and notes reported by me at the hearing in the above case before the Office of Special Masters. Date: June 22, 2007 Christina Chesley Official Reporter Heritage Reporting Corporation Suite 600 1220 L Street, N.W. Washington, D.C. 20005-4018 Heritage Reporting Corporation (202) 628-4888


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